Co-reporter:Ksenia Timachova;Mahati Chintapalli;Kevin R. Olson;Sue J. Mecham;Nitash P. Balsara
Soft Matter (2005-Present) 2017 vol. 13(Issue 32) pp:5389-5396
Publication Date(Web):2017/08/16
DOI:10.1039/C7SM00794A
Perfluoropolyethers (PFPEs) are polymer electrolytes with fluorinated carbon backbones that have high flash points and have been shown to exhibit moderate conductivities and high cation transference numbers when mixed with lithium salts. Ion transport in four PFPE electrolytes with different endgroups was characterized by differential scanning calorimetry (DSC), ac impedance, and pulsed-field gradient NMR (PFG-NMR) as a function of salt concentration and temperature. In spite of the chemical similarity of the electrolytes, salt diffusion coefficients measured by PFG-NMR and the glass transition temperature measured by DSC appear to be uncorrelated to ionic conductivity measured by ac impedance. We calculate a non-dimensional parameter, β, that depends on the salt diffusion coefficients and ionic conductivity. We also use the Vogel–Tammann–Fulcher relationship to fit the temperature dependence of conductivity. We present a linear relationship between the prefactor in the VTF fit and β; both parameters vary by four orders of magnitude in our experimental window. Our analysis suggests that transport in electrolytes with low dielectric constants (low β) is dictated by ion hopping between clusters.
Co-reporter:Charles J. Bowerman, James D. Byrne, Kevin S. Chu, Allison N. Schorzman, Amanda W. Keeler, Candice A. Sherwood, Jillian L. Perry, James C. Luft, David B. Darr, Allison M. Deal, Mary E. Napier, William C. Zamboni, Norman E. Sharpless, Charles M. Perou, and Joseph M. DeSimone
Nano Letters 2017 Volume 17(Issue 1) pp:
Publication Date(Web):December 14, 2016
DOI:10.1021/acs.nanolett.6b03971
Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. This GEMM recapitulates the genetics of the human disease and is reflective of patient outcome and, therefore, better represents the clinical impact of new therapeutics. Pharmacokinetic analysis showed that delivery of these PLGA-docetaxel nanoparticles increased docetaxel circulation time and provided similar docetaxel exposure to tumor compared to the clinical formulation of docetaxel, Taxotere. These PLGA-docetaxel nanoparticles improved tumor growth inhibition and significantly increased median survival time. This study demonstrates the potential of nanotechnology to improve the therapeutic index of chemotherapies and rescue therapeutic efficacy to treat nonresponsive cancers.Keywords: chemoresistance; docetaxel; genetically engineered mouse model; Nanoparticles; triple-negative breast cancer;
Co-reporter:Khosrow Khodabehlou;Shaomin Tian;James C. Luft;Saad A. Khan
Advanced Healthcare Materials 2016 Volume 5( Issue 6) pp:653-658
Publication Date(Web):
DOI:10.1002/adhm.201500797
Co-reporter:Chintan H. Kapadia, Shaomin Tian, Jillian L. Perry, J. Christopher Luft, and Joseph M. DeSimone
Molecular Pharmaceutics 2016 Volume 13(Issue 10) pp:3381-3394
Publication Date(Web):August 23, 2016
DOI:10.1021/acs.molpharmaceut.6b00288
Educating our immune system via vaccination is an attractive approach to combat infectious diseases. Eliciting antigen specific cytotoxic T cells (CTLs), CD8+ effector T cells, is essential in controlling intracellular infectious diseases such as influenza (Flu), tuberculosis (TB), hepatitis, and HIV/AIDS, as well as tumors. However, vaccination utilizing subunit peptides to elicit a potent CD8+ T cell response with antigenic peptides is typically ineffective due to poor immunogenicity. Here we have engineered a reduction sensitive nanoparticle (NP) based subunit vaccine for intracellular delivery of an antigenic peptide and immunostimulatory adjuvant. We have co-conjugated an antigenic peptide (ovalbumin-derived CTL epitope [OVA257–264: SIINFEKL]) and an immunostimulatory adjuvant (CpG ODNs, TLR9 agonist) to PEG hydrogel NPs via a reduction sensitive linker. Bone-marrow derived dendritic cells (BMDCs) treated with the SIINFEKL conjugated NPs efficiently cross-presented the antigenic peptide via MHC-I surface receptor and induced proliferation of OT-I T cells. CpG ODN-conjugated NPs induced maturation of BMDCs as evidenced by the overexpression of CD80 and CD40 costimulatory receptors. Moreover, codelivery of NP conjugated SIINFEKL and CpG ODN significantly increased the frequency of IFN-γ producing CD8+ effector T cells in mice (∼6-fold improvement over soluble antigen and adjuvant). Furthermore, the NP subunit vaccine-induced effector T cells were able to kill up to 90% of the adoptively transferred antigenic peptide-loaded target cell. These results demonstrate that the reduction sensitive NP subunit vaccine elicits a potent CTL response and provide compelling evidence that this approach could be utilized to engineer particulate vaccines to deliver tumor or pathogen associated antigenic peptides to harness the immune system to fight against cancer and infectious diseases.Keywords: cancer vaccine; cytotoxic T cells (CTL); disulfide linkers; nanoparticles; peptide vaccine;
Co-reporter:Tojan B. Rahhal; Catherine A. Fromen; Erin M. Wilson; Marc P. Kai; Tammy W. Shen; J. Christopher Luft
Molecular Pharmaceutics 2016 Volume 13(Issue 5) pp:1626-1635
Publication Date(Web):March 24, 2016
DOI:10.1021/acs.molpharmaceut.6b00066
Pulmonary delivery has great potential for delivering biologics to the lung if the challenges of maintaining activity, stability, and ideal aerosol characteristics can be overcome. To study the interactions of a biologic in the lung, we chose butyrylcholinesterase (BuChE) as our model enzyme, which has application for use as a bioscavenger protecting against organophosphate exposure or for use with pseudocholinesterase deficient patients. In mice, orotracheal administration of free BuChE resulted in 72 h detection in the lungs and 48 h in the broncheoalveolar lavage fluid (BALF). Free BuChE administered to the lung of all mouse backgrounds (Nude, C57BL/6, and BALB/c) showed evidence of an acute cytokine (IL-6, TNF-α, MIP2, and KC) and cellular immune response that subsided within 48 h, indicating relatively safe administration of this non-native biologic. We then developed a formulation of BuChE using Particle Replication in Non-Wetting Templates (PRINT). Aerosol characterization demonstrated biologically active BuChE 1 μm cylindrical particles with a mass median aerodynamic diameter of 2.77 μm, indicative of promising airway deposition via dry powder inhalers (DPI). Furthermore, particulate BuChE delivered via dry powder insufflation showed residence time of 48 h in the lungs and BALF. The in vivo residence time, immune response, and safety of particulate BuChE delivered via a pulmonary route, along with the cascade impaction distribution of dry powder PRINT BuChE, showed promise in the ability to deliver active enzymes with ideal deposition characteristics. These findings provide evidence for the feasibility of optimizing the use of BuChE in the clinic; PRINT BuChE particles can be readily formulated for use in DPIs, providing a convenient and effective treatment option.
Co-reporter:Catherine A. Fromen, Tojan B. Rahhal, Gregory R. Robbins, Marc P. Kai, Tammy W. Shen, J. Christopher Luft, Joseph M. DeSimone
Nanomedicine: Nanotechnology, Biology and Medicine 2016 Volume 12(Issue 3) pp:677-687
Publication Date(Web):April 2016
DOI:10.1016/j.nano.2015.11.002
Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles. Instillation of cationic nanoparticles resulted in the upregulation of Ccl2 and Cxc10, which likely contributes to the recruitment of CD11b DCs to the lung. In total, these cellular mechanisms explain the increased efficacy of cationic formulations as a pulmonary vaccine carrier and provide critical benchmarks in the design of pulmonary vaccine nanoparticles.From the Clinical EditorAdvance in nanotechnology has allowed the production of precise nanoparticles as vaccines. In this regard, pulmonary delivery has the most potential. In this article, the authors investigated the interaction of nanoparticles with various types of lung antigen presenting cells in an attempt to understand the cellular mechanisms. The findings would further help the future design of much improved vaccines for clinical use.Nanoparticle surface charge is a key parameter in the recruitment and association of pulmonary antigen presenting cells following respiratory administration, resulting in increased cytokine and chemokine production necessary for an effective lung vaccine. Pulmonary delivery of PRINT® cationic nanoparticles resulted in an increased local immune response and preferential association with dendritic cells compared to PRINT® anionic nanoparticle administration.
Co-reporter:Amanda W. Keeler;J. Christopher Luft;Allison N. Schorzman;William C. Zamboni;Mohammad R. N. Jajja;James D. Byrne;Jen Jen Yeh
PNAS 2016 Volume 113 (Issue 8 ) pp:2200-2205
Publication Date(Web):2016-02-23
DOI:10.1073/pnas.1600421113
Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen
of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment
of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted
directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery
of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery
of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially
lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition
compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability
of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery.
Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic
disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to
improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.
Co-reporter:Mahati Chintapalli, Ksenia Timachova, Kevin R. Olson, Sue J. Mecham, Didier Devaux, Joseph M. DeSimone, and Nitash P. Balsara
Macromolecules 2016 Volume 49(Issue 9) pp:3508-3515
Publication Date(Web):April 29, 2016
DOI:10.1021/acs.macromol.6b00412
Connecting continuum-scale ion transport properties such as conductivity and cation transference number to microscopic transport properties such as ion dissociation and ion self-diffusivities is an unresolved challenge in characterizing polymer electrolytes. Better understanding of the relationship between microscopic and continuum scale transport properties would enable the rational design of improved electrolytes for applications such as lithium batteries. We present measurements of continuum and microscopic ion transport properties of nonflammable liquid electrolytes consisting of binary mixtures of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and perfluoropolyethers (PFPE) with different end groups: diol, dimethyl carbonate, ethoxy–diol, and ethoxy–dimethyl carbonate. The continuum properties, conductivity and cation transference number, were measured by ac impedance spectroscopy and potentiostatic polarization, respectively. The ion self-diffusivities were measured by pulsed field gradient nuclear magnetic resonance spectroscopy (PFG-NMR), and a microscopic cation transference number was calculated from these measurements. The measured ion self-diffusivities did not reflect the measured conductivities; in some cases, samples with high diffusivities exhibited low conductivity. We introduce a nondimensional parameter, β, that combines microscopic diffusivities and conductivity. We show that β is a sensitive function of end-group chemistry. In the ethoxylated electrolytes, β is close to unity, the value expected for electrolytes that obey the Nernst–Einstein equation. In these cases, the microscopic and continuum transference numbers are in reasonable agreement. PFPE electrolytes devoid of ethoxy groups exhibit values of β that are significantly lower than unity. In these cases, there is significant deviation between microscopic and continuum transference numbers. We propose that this may be due to electrostatic coupling of the cation and anion or contributions to the NMR signal from neutral ion pairs.
Co-reporter:Irune Villaluenga;Kevin H. Wujcik;Didier Devaux;Wei Tong;Dominica H. C. Wong;Nitash P. Balsara
PNAS 2016 Volume 113 (Issue 1 ) pp:52-57
Publication Date(Web):2016-01-05
DOI:10.1073/pnas.1520394112
Despite high ionic conductivities, current inorganic solid electrolytes cannot be used in lithium batteries because of a lack
of compliance and adhesion to active particles in battery electrodes as they are discharged and charged. We have successfully
developed a compliant, nonflammable, hybrid single ion-conducting electrolyte comprising inorganic sulfide glass particles
covalently bonded to a perfluoropolyether polymer. The hybrid with 23 wt% perfluoropolyether exhibits low shear modulus relative
to neat glass electrolytes, ionic conductivity of 10−4 S/cm at room temperature, a cation transference number close to unity, and an electrochemical stability window up to 5 V
relative to Li+/Li. X-ray absorption spectroscopy indicates that the hybrid electrolyte limits lithium polysulfide dissolution and is, thus,
ideally suited for Li-S cells. Our work opens a previously unidentified route for developing compliant solid electrolytes
that will address the challenges of lithium batteries.
Co-reporter:Marc P. Kai, Hailey E. Brighton, Catherine A. Fromen, Tammy W. Shen, J. Christopher Luft, Yancey E. Luft, Amanda W. Keeler, Gregory R. Robbins, Jenny P. Y. Ting, William C. Zamboni, James E. Bear, and Joseph M. DeSimone
ACS Nano 2016 Volume 10(Issue 1) pp:861
Publication Date(Web):November 23, 2015
DOI:10.1021/acsnano.5b05999
Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.Keywords: immunology; intravital; nanoparticle; orthotopic; pharmacokinetic;
Co-reporter:Kevin G. Reuter, Jillian L. Perry, Dongwook Kim, J. Christopher Luft, Rihe Liu, and Joseph M. DeSimone
Nano Letters 2015 Volume 15(Issue 10) pp:6371-6378
Publication Date(Web):September 21, 2015
DOI:10.1021/acs.nanolett.5b01362
In this Letter, we varied targeting ligand density of an EGFR binding affibody on the surface of two different hydrogel PRINT nanoparticles (80 nm × 320 and 55 nm × 60 nm) and monitored effects on target-cell association, off-target phagocytic uptake, biodistribution, and tumor accumulation. Interestingly, variations in ligand density only significantly altered in vitro internalization rates for the 80 nm × 320 nm particle. However, in vivo, both particle sizes experienced significant changes in biodistribution and pharmacokinetics as a function of ligand density. Overall, nanoparticle size and passive accumulation were the dominant factors eliciting tumor sequestration.
Co-reporter:Dominica H. C. Wong, Alessandra Vitale, Didier Devaux, Austria Taylor, Ashish A. Pandya, Daniel T. Hallinan, Jacob L. Thelen, Sue J. Mecham, Simon F. Lux, Alexander M. Lapides, Paul R. Resnick, Thomas J. Meyer, Robert M. Kostecki, Nitash P. Balsara, and Joseph M. DeSimone
Chemistry of Materials 2015 Volume 27(Issue 2) pp:597
Publication Date(Web):December 20, 2014
DOI:10.1021/cm504228a
Electrolytes consisting of low molecular weight perfluoropolyether (PFPE), poly(ethylene glycol) (PEG), and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) blends were prepared and systematically studied for salt concentration and stoichiometry effects on the materials’ thermal and electrochemical properties. Herein we report that the tunable ratios of PFPE and PEG allow for precise control of crystalline melting and glass transition temperature properties. These blended liquid polymer electrolytes are inherently nonflammable and remain stable in the amorphous phase from approximately 150 °C down to −85 °C. The ionic conductivity of the electrolytes are on the order of 10–4 S/cm at 30 °C, which makes them suitable for rechargeable lithium batteries.
Co-reporter:Khosrow Khodabandehlou, Amar S. Kumbhar, Sohrab Habibi, Ashish A. Pandya, J. Christopher Luft, Saad A. Khan, and Joseph M. DeSimone
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 10) pp:5756
Publication Date(Web):March 5, 2015
DOI:10.1021/am508520z
With the recent advances in the development of novel protein based therapeutics, controlled delivery of these biologics is an important area of research. Herein, we report the synthesis of microparticles from bovine serum albumin (BSA) as a model protein using Particle Replication in Non-wetting Templates (PRINT) with specific size and shape. These particles were functionalized at room temperature using multifunctional chlorosilane that cross-link the particles to render them to slowly-dissolving in aqueous media. Mass spectrometric study of the reaction products of diisopropyldichlorosilane with individual components of the particles revealed that they are capable of reacting and forming cross-links. Energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were also used to confirm the functionalization of the particles. Cross sectional analysis using focused ion beam (FIB) and EDS proved that the functionalization occurs throughout the bulk of the particles and is not just limited to the surface. Circular dichroism data confirmed that the fraction of BSA molecules released from the particles retains its secondary structure thereby indicating that the system can be used for delivering protein based formulations while controlling the dissolution kinetics.Keywords: bovine serum albumin; controlled release; diisopropyldichlorosilane; functionalization; protein delivery; silylation
Co-reporter:Marc P. Kai, Amanda W. Keeler, Jillian L. Perry, Kevin G. Reuter, J. Christopher Luft, Sara K. O'Neal, William C. Zamboni, Joseph M. DeSimone
Journal of Controlled Release 2015 Volume 204() pp:70-77
Publication Date(Web):28 April 2015
DOI:10.1016/j.jconrel.2015.03.001
Cisplatin is a cytotoxic drug used as a first-line therapy for a wide variety of cancers. However, significant renal and neurological toxicities limit its clinical use. It has been documented that drug toxicities can be mitigated through nanoparticle formulation, while simultaneously increasing tumor accumulation through the enhanced permeation and retention effect. Circulation persistence is a key characteristic for exploiting this effect, and to that end we have developed long-circulating, PEGylated, polymeric hydrogels using the Particle Replication In Non-wetting Templates (PRINT®) platform and complexed cisplatin into the particles (PRINT-Platin). Sustained release was demonstrated, and drug loading correlated to surface PEG density. A PEG Mushroom conformation showed the best compromise between particle pharmacokinetic (PK) parameters and drug loading (16 wt.%). While the PK profile of PEG Brush was superior, the loading was poor (2 wt.%). Conversely, the drug loading in non-PEGylated particles was better (20 wt.%), but the PK was not desirable. We also showed comparable cytotoxicity to cisplatin in several cancer cell lines (non-small cell lung, A549; ovarian, SKOV-3; breast, MDA-MB-468) and a higher MTD in mice (10 mg/kg versus 5 mg/kg). The pharmacokinetic profiles of drug in plasma, tumor, and kidney indicate improved exposure in the blood and tumor accumulation, with concurrent renal protection, when cisplatin was formulated in a nanoparticle. PK parameters were markedly improved: a 16.4-times higher area-under-the-curve (AUC), a reduction in clearance (CL) by a factor of 11.2, and a 4.20-times increase in the volume of distribution (Vd). Additionally, non-small cell lung and ovarian tumor AUC was at least twice that of cisplatin in both models. These findings suggest the potential for PRINT-Platin to improve efficacy and reduce toxicity compared to current cisplatin therapies.
Co-reporter:Da Ma; Shaomin Tian; Jeremy Baryza; J. Christopher Luft▲▲◆●■□
Molecular Pharmaceutics 2015 Volume 12(Issue 10) pp:3518-3526
Publication Date(Web):August 19, 2015
DOI:10.1021/acs.molpharmaceut.5b00054
To achieve the great potential of siRNA based gene therapy, safe and efficient systemic delivery in vivo is essential. Here we report reductively responsive hydrogel nanoparticles with highly uniform size and shape for systemic siRNA delivery in vivo. “Blank” hydrogel nanoparticles with high aspect ratio were prepared using continuous particle fabrication based on PRINT (particle replication in nonwetting templates). Subsequently, siRNA was conjugated to “blank” nanoparticles via a disulfide linker with a high loading ratio of up to 18 wt %, followed by surface modification to enhance transfection. This fabrication process could be easily scaled up to prepare large quantity of hydrogel nanoparticles. By controlling hydrogel composition, surface modification, and siRNA loading ratio, siRNA conjugated nanoparticles were highly tunable to achieve high transfection efficiency in vitro. FVII-siRNA conjugated nanoparticles were further stabilized with surface coating for in vivo siRNA delivery to liver hepatocytes, and successful gene silencing was demonstrated at both mRNA and protein levels.
Co-reporter:Sarah N. Mueller; Shaomin Tian
Molecular Pharmaceutics 2015 Volume 12(Issue 5) pp:1356-1365
Publication Date(Web):March 28, 2015
DOI:10.1021/mp500589c
Nanoparticle delivery of subunit vaccines may increase vaccine efficacy, leading to a wide variety of safe and effective vaccines beyond those available through dosing inactivated or live, attenuated whole pathogens. Here we present a versatile vaccine delivery platform based on PRINT hydrogels made of biocompatible hydroxy-poly(ethylene glycol) (PEG) that is able to activate the complement system by the alternative pathway. These lymph node targeting nanoparticles (NPs) promote the immunogenicity of a model antigen, ovalbumin, showing comparable adjuvant effect to alum. We demonstrate that an antigen-specific humoral response is correlated with antigen delivery to the draining lymph nodes, in particular, B cell rich regions of the lymph nodes. 80 × 180 nm cylindrical NPs were able to sustain prolonged antigen presentation to antigen presenting cells (APCs) and elicit a stronger immune response than nondraining 1 × 1 μm NPs or rapidly clearing soluble antigen. The 80 × 180 nm NPs also show high levels of uptake by key APCs and efficiently stimulate CD4+ helper T cell proliferation in vivo, further promoting antibody production. These features together produce a significant humoral immune response, superior to that produced by free antigen alone. The simplicity of the chemistries used in antigen conjugation to PRINT NPs confers versatility to this antigen delivery platform, allowing for potential application to many infectious diseases.
Co-reporter:Adrian T. O’Neill;Kyle Wagner;Nabeel Hyder;Mohammad N. R. Jajja;Ryan E. Little;Amanda W. Keeler;David Darr;Richard A. Moffitt;Colleen Stack;James D. Byrne;Meredith Nelson;Allison Deal;Carey K. Anders;Lissett R. Bickford;Joel E. Tepper;Andrew Z. Wang;Richard Stack;Christopher R. Brooks;William Lee;J. Chris Luft;Mary E. Napier;Jen Jen Yeh;William C. Zamboni
Science Translational Medicine 2015 Volume 7(Issue 273) pp:
Publication Date(Web):
DOI:10.1126/scitranslmed.3009951
Local administration of cytotoxic drugs using iontophoresis results in drug accumulation and therapeutic efficacy in mouse models of pancreatic and breast cancer and favorable PK in a large animal model.
Co-reporter:Gregory R. Robbins;Catherine A. Fromen;Marc P. Kai;Tammy W. Shen;Jenny P. Y. Ting
PNAS 2015 Volume 112 (Issue 2 ) pp:488-493
Publication Date(Web):2015-01-13
DOI:10.1073/pnas.1422923112
Pulmonary immunization enhances local humoral and cell-mediated mucosal protection, which are critical for vaccination against
lung-specific pathogens such as influenza or tuberculosis. A variety of nanoparticle (NP) formulations have been tested preclinically
for pulmonary vaccine development, yet the role of NP surface charge on downstream immune responses remains poorly understood.
We used the Particle Replication in Non-Wetting Templates (PRINT) process to synthesize hydrogel NPs that varied only in surface
charge and otherwise maintained constant size, shape, and antigen loading. Pulmonary immunization with ovalbumin (OVA)-conjugated
cationic NPs led to enhanced systemic and lung antibody titers compared with anionic NPs. Increased antibody production correlated
with robust germinal center B-cell expansion and increased activated CD4+ T-cell populations in lung draining lymph nodes. Ex vivo treatment of dendritic cells (DCs) with OVA-conjugated cationic
NPs induced robust antigen-specific T-cell proliferation with ∼100-fold more potency than soluble OVA alone. Enhanced T-cell
expansion correlated with increased expression of surface MHCII, T-cell coactivating receptors, and key cytokines/chemokine
expression by DCs treated with cationic NPs, which were not observed with anionic NPs or soluble OVA. Together, these studies
highlight the importance of NP surface charge when designing pulmonary vaccines, and our findings support the notion that
cationic NP platforms engender potent humoral and mucosal immune responses.
Co-reporter:Tammy W. Shen;Catherine A. Fromen;Marc P. Kai
Pharmaceutical Research 2015 Volume 32( Issue 10) pp:3248-3260
Publication Date(Web):2015 October
DOI:10.1007/s11095-015-1701-7
We evaluated the role of a poly(ethylene glycol) (PEG) surface
coating to increase residence times and alter the cellular fate of nano- and
microparticles delivered to the lung.Three sizes of PRINT hydrogel particles (80 × 320 nm, 1.5 and 6 μm
donuts) with and without a surface PEG coating were instilled in the airways of
C57/b6 mice. At time points of 1, 7, and 28 days, BALF and whole lungs were
evaluated for the inflammatory cytokine Il-6 and chemokine MIP-2,
histopathology, cellular populations of macrophages, dendritic cells (DCs), and
granulocytes, and particulate uptake within these cells through flow cytometry,
ELISAs, and fluorescent imaging.Particles of all sizes and surface chemistries were readily observed
in the lung with minimal inflammatory response at all time points. Surface
modification with PEGylation was found to significantly increase lung residence
times and homogeneous lung distribution, delaying macrophage clearance of all
sizes, with the largest increase in residence time observed for 80 × 320 nm
particles. Additionally, it was observed that DCs were recruited to the airway
following administration of unPEGylated particles and preferentially associated
with these particles.Pulmonary drug delivery vehicles designed with a PEG surface coating
can be used to delay particle uptake and promote cell-specific targeting of
therapeutics.
Co-reporter:Kevin S. Chu, Mathew C. Finniss, Allison N. Schorzman, Jennifer L. Kuijer, J. Christopher Luft, Charles J. Bowerman, Mary E. Napier, Zishan A. Haroon, William C. Zamboni, and Joseph M. DeSimone
Nano Letters 2014 Volume 14(Issue 3) pp:1472-1476
Publication Date(Web):February 20, 2014
DOI:10.1021/nl4046558
Delivery systems designed to have triggered release after passively targeting the tumor may improve small molecule chemotherapeutic delivery. Particle replication in nonwetting templates was used to prepare nanoparticles to passively target solid tumors in an A549 subcutaneous xenograft model. An acid labile prodrug was delivered to minimize systemic free docetaxel concentrations and improve tolerability without compromising efficacy.
Co-reporter:Kai Chen ; Jing Xu ; J. Christopher Luft ; Shaomin Tian ; Jay S. Raval ⊗
Journal of the American Chemical Society 2014 Volume 136(Issue 28) pp:9947-9952
Publication Date(Web):June 18, 2014
DOI:10.1021/ja503939n
Lowering the modulus of hydrogel particles could enable them to bypass in vivo physical barriers that would otherwise filter particles with similar size but higher modulus. Incorporation of electrolyte moieties into the polymer network of hydrogel particles to increase the swelling ratio is a straightforward and quite efficient way to decrease the modulus. In addition, charged groups in hydrogel particles can also help secure cargoes. However, the distribution of charged groups on the surface of a particle can accelerate the clearance of particles. Herein, we developed a method to synthesize highly swollen microgels of precise size with near-neutral surface charge while retaining interior charged groups. A strategy was employed to enable a particle to be highly cross-linked with very small mesh size, and subsequently PEGylated to quench the exterior amines only without affecting the internal amines. Acidic degradation of the cross-linker allows for swelling of the particles to microgels with a desired size and deformability. The microgels fabricated demonstrated extended circulation in vivo compared to their counterparts with a charged surface, and could potentially be utilized in in vivo applications including as oxygen carriers or nucleic acid scavengers.
Co-reporter:Mathew C. Finniss, Kevin S. Chu, Charles J. Bowerman, J. Christopher Luft, Zishan A. Haroon and Joseph M. DeSimone
MedChemComm 2014 vol. 5(Issue 9) pp:1355-1358
Publication Date(Web):16 Jun 2014
DOI:10.1039/C4MD00150H
Antibody drug conjugates (ADC) couple therapeutic monoclonal antibodies (mAb) with potent toxins through a linker that is stable within systemic circulation, but cleaves within the target cells. In this report, silyl ether chemistry was used to couple the mAb trastuzumab with the chemotherapeutic, gemcitabine, to demonstrate the use of silyl ethers as a potential linker for ADCs.
Co-reporter:Jacob L. Thelen;Vincent S. Battaglia;Dominica H. C. Wong;Ashish A. Pandya;Didier Devaux;Yanbao Fu;Nitash P. Balsara
PNAS 2014 Volume 111 (Issue 9 ) pp:3327-3331
Publication Date(Web):2014-03-04
DOI:10.1073/pnas.1314615111
The flammability of conventional alkyl carbonate electrolytes hinders the integration of large-scale lithium-ion batteries
in transportation and grid storage applications. In this study, we have prepared a unique nonflammable electrolyte composed
of low molecular weight perfluoropolyethers and bis(trifluoromethane)sulfonimide lithium salt. These electrolytes exhibit
thermal stability beyond 200 °C and a remarkably high transference number of at least 0.91 (more than double that of conventional
electrolytes). Li/LiNi1/3Co1/3Mn1/3O2 cells made with this electrolyte show good performance in galvanostatic cycling, confirming their potential as rechargeable
lithium batteries with enhanced safety and longevity.
Co-reporter:Katherine A. Moga;Lissett R. Bickford;Robert D. Geil;Stuart S. Dunn;Ashish A. Pya;Yapei Wang;John H. Fain;Christine F. Archuleta;Adrian T. O'Neill
Advanced Materials 2013 Volume 25( Issue 36) pp:5060-5066
Publication Date(Web):
DOI:10.1002/adma.201300526
Co-reporter:Stuart S. Dunn, James D. Byrne, Jillian L. Perry, Kai Chen, and Joseph M. DeSimone
ACS Macro Letters 2013 Volume 2(Issue 5) pp:393
Publication Date(Web):April 24, 2013
DOI:10.1021/mz400116a
The complexity of tumor biology warrants tailored drug delivery for overcoming the major challenges faced by cancer therapies. The versatility of the PRINT (Particle Replication In Nonwetting Templates) process has enabled the preparation of shape- and size-specific particles with a wide range of chemical compositions and therapeutic cargos. Different particle matrices and drugs may be combined in a plug-and-play approach, such that physicochemical characteristics of delivery vectors may be optimized for biocompatibility, cargo stability, and release, circulation half-life, and efficacy. Thus, the engineering of particles for cancer therapy with specific biophysical behaviors and cellular responses has been demonstrated via the PRINT process.
Co-reporter:Jing Xu, J. Christopher Luft, Xianwen Yi, Shaomin Tian, Gary Owens, Jin Wang, Ashley Johnson, Peter Berglund, Jonathan Smith, Mary E. Napier, and Joseph M. DeSimone
Molecular Pharmaceutics 2013 Volume 10(Issue 9) pp:3366-3374
Publication Date(Web):August 7, 2013
DOI:10.1021/mp400190z
Herein we report the development of a nonviral lipid-complexed PRINT (particle replication in nonwetting templates) protein particle system (LPP particle) for RNA replicon delivery with a view toward RNA replicon-based vaccination. Cylindrical bovine serum albumin (BSA) particles (diameter (d) 1 μm, height (h) 1 μm) loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology. Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that (1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines and (2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles.Keywords: gene delivery; lipid; PRINT; protein particle; RNA replicon;
Co-reporter:Kevin S. Chu, Warefta Hasan, Sumit Rawal, Mark D. Walsh, Elizabeth M. Enlow, J. Christopher Luft, Arlene S. Bridges, Jennifer L. Kuijer, Mary E. Napier, William C. Zamboni, Joseph M. DeSimone
Nanomedicine: Nanotechnology, Biology and Medicine 2013 Volume 9(Issue 5) pp:686-693
Publication Date(Web):July 2013
DOI:10.1016/j.nano.2012.11.008
The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter = 80 nm; height = 320 nm (PRINT-Doc-80×320) and d = 200 nm; h = 200 nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~ 20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~ 18-fold (PRINT-Doc-80×320) and ~ 33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently led to increased tumor exposure of Docetaxel from 0 to 168 h (~ 53% higher for PRINT-Doc-80×320 and ~ 76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.From the Clinical EditorIn this study, the plasma, tumor, and tissue pharmacokinetics of different Docetaxel nanoparticles of precise shape and size were characterized in mice with human ovarian carcinoma xenograft. It is concluded that the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.The top-down particle fabrication technique Particle Replication in Non-Wetting Templates (PRINT®) was used to fabricate size and shape specific nanoparticles containing docetaxel. A size–shape dependent docetaxel distribution was observed when particles were dosed to mice bearing human ovarian carcinoma cells. The particle with the smaller diameter (d = 80 nm versus d = 200 nm) had less docetaxel distribution into the spleen, liver and lungs but higher accumulation in the tumor from 0 to 24 h.
Co-reporter:Kevin S. Chu, Allison N. Schorzman, Mathew C. Finniss, Charles J. Bowerman, Lei Peng, James C. Luft, Andrew J. Madden, Andrew Z. Wang, William C. Zamboni, Joseph M. DeSimone
Biomaterials 2013 34(33) pp: 8424-8429
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.07.038
Co-reporter:Warefta Hasan, Kevin Chu, Anuradha Gullapalli, Stuart S. Dunn, Elizabeth M. Enlow, J. Christopher Luft, Shaomin Tian, Mary E. Napier, Patrick D. Pohlhaus, Jason P. Rolland, and Joseph M. DeSimone
Nano Letters 2012 Volume 12(Issue 1) pp:287-292
Publication Date(Web):December 14, 2011
DOI:10.1021/nl2035354
Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32–46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.
Co-reporter:Jillian L. Perry, Kevin G. Reuter, Marc P. Kai, Kevin P. Herlihy, Stephen W. Jones, J. Chris Luft, Mary Napier, James E. Bear, and Joseph M. DeSimone
Nano Letters 2012 Volume 12(Issue 10) pp:5304-5310
Publication Date(Web):August 27, 2012
DOI:10.1021/nl302638g
In this account, we varied PEGylation density on the surface of hydrogel PRINT nanoparticles and systematically observed the effects on protein adsorption, macrophage uptake, and circulation time. Interestingly, the density of PEGylation necessary to promote a long-circulating particle was dramatically less than what has been previously reported. Overall, our methodology provides a rapid screening technique to predict particle behavior in vivo and our results deliver further insight to what PEG density is necessary to facilitate long-circulation.
Co-reporter:Stuart S. Dunn ; Shaomin Tian ; Steven Blake ; Jin Wang ; Ashley L. Galloway ; Andrew Murphy ; Patrick D. Pohlhaus ; Jason P. Rolland ; Mary E. Napier ▲◆●■□
Journal of the American Chemical Society 2012 Volume 134(Issue 17) pp:7423-7430
Publication Date(Web):April 5, 2012
DOI:10.1021/ja300174v
A critical need still remains for effective delivery of RNA interference (RNAi) therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based systems have been most extensively explored for transfection with small interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility of materials implemented in delivery systems must be ensured to maximize therapeutic indices. Hydrogel nanoparticles of defined dimensions and compositions, prepared via a particle molding process that is a unique off-shoot of soft lithography known as particle replication in nonwetting templates (PRINT), were explored in these studies as delivery vectors. Initially, siRNA was encapsulated in particles through electrostatic association and physical entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation of cargo from particles after systemic administration or during postfabrication processing for surface functionalization, a polymerizable siRNA pro-drug conjugate with a degradable, disulfide linkage was prepared. Triggered release of siRNA from the pro-drug hydrogels was observed under a reducing environment while cargo retention and integrity were maintained under physiological conditions. Gene silencing efficiency and cytocompatibility were optimized by screening the amine content of the particles. When appropriate control siRNA cargos were loaded into hydrogels, gene knockdown was only encountered for hydrogels containing releasable, target-specific siRNAs, accompanied by minimal cell death. Further investigation into shape, size, and surface decoration of siRNA-conjugated hydrogels should enable efficacious targeted in vivo RNAi therapies.
Co-reporter:Jing Xu ; Jin Wang ; J. Christopher Luft ⊗; Shaomin Tian ⊗; Gary Owens ; Jr.; Ashish A. Pandya ⊗; Peter Berglund ; Patrick Pohlhaus ; Benjamin W. Maynor ; Jonathan Smith ; Bolyn Hubby ; Mary E. Napier ⊗× +⊗◆
Journal of the American Chemical Society 2012 Volume 134(Issue 21) pp:8774-8777
Publication Date(Web):May 8, 2012
DOI:10.1021/ja302363r
Herein, we report the fabrication of protein (bovine serum albumin, BSA) particles which were rendered transiently insoluble using a novel, reductively labile disulfide-based cross-linker. After being cross-linked, the protein particles retain their integrity in aqueous solution and dissolve preferentially under a reducing environment. Our data demonstrates that cleavage of the cross-linker leaves no chemical residue on the reactive amino group. Delivery of a self-replicating RNA was achieved via the transiently insoluble PRINT protein particles. These protein particles can provide new opportunities for drug and gene delivery.
Co-reporter:Timothy J. Merkel, Kai Chen, Stephen W. Jones, Ashish A. Pandya, Shaomin Tian, Mary E. Napier, William E. Zamboni, Joseph M. DeSimone
Journal of Controlled Release 2012 Volume 162(Issue 1) pp:37-44
Publication Date(Web):20 August 2012
DOI:10.1016/j.jconrel.2012.06.009
There is a growing recognition that the deformability of particles used for drug delivery plays a significant role on their biodistribution and circulation profile. Understanding these effects would provide a crucial tool for the rational design of drug delivery systems. While particles resembling red blood cells (RBCs) in size, shape and deformability have extended circulation times and altered biodistribution profiles compared to rigid, but otherwise similar particles, the in vivo behavior of such highly deformable particles of varied size has not been explored. We report the fabrication of a series of discoid, monodisperse, low-modulus hydrogel particles with diameters ranging from 0.8 to 8.9 μm, spanning sizes smaller than and larger than RBCs. We injected these particles into healthy mice, and tracked their concentration in the blood and their distribution into major organs. These deformable particles all demonstrated some hold up in filtration tissues like the lungs and spleen, followed by release back into the circulation, characterized by decreases in particles in these tissues with concomitant increases in particle concentration in blood. Particles similar to red blood cells in size demonstrated longer circulation times, suggesting that this size and shape of deformable particle is uniquely suited to avoid clearance.
Co-reporter:Farrell R. Kersey, Timothy J. Merkel, Jillian L. Perry, Mary E. Napier, and Joseph M. DeSimone
Langmuir 2012 Volume 28(Issue 23) pp:8773-8781
Publication Date(Web):May 21, 2012
DOI:10.1021/la301279v
We describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT (particle replication in nonwetting templates). The nanoparticles possess a constant width of 80 nm, and we varied their lengths ranging from 180 to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix. Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 μm pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy. The results show that particle recovery is mostly independent of aspect ratio at all cross-linker concentrations utilized, with the exception of 96 wt % PEG diacrylate 80 × 5000 nm particles, which showed the lowest percent recovery.
Co-reporter:Elizabeth M. Enlow, J. Christopher Luft, Mary E. Napier, and Joseph M. DeSimone
Nano Letters 2011 Volume 11(Issue 2) pp:808-813
Publication Date(Web):January 25, 2011
DOI:10.1021/nl104117p
Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT (particle replication in nonwetting templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere.
Co-reporter:Jie-Yu Wang ; Yapei Wang ; Sergei S. Sheiko ; Douglas E. Betts
Journal of the American Chemical Society 2011 Volume 134(Issue 13) pp:5801-5806
Publication Date(Web):October 11, 2011
DOI:10.1021/ja2066187
New methods to direct the self-assembly of particles are highly sought after for multiple applications, including photonics, electronics, and drug delivery. Most techniques, however, are limited to chemical patterning on spherical particles, limiting the range of possible structures. We developed a lithographic technique for fabrication of chemically anisotropic rod-like particles in which we can specify both the size and shape of particles and implement multiple diverse materials to control interfacial interactions. Multiphase rod-like particles, including amphiphilic diblock, triblock, and multiblock were fabricated in the same template mold having a tunable hydrophilic/hydrophobic ratio. Self-assembly of diblock or triblock rods at a water/oil interface led to the formation of bilayer or ribbon-like structures.
Co-reporter:Yapei Wang, John A. Finlay, Douglas E. Betts, Timothy J. Merkel, J. Christopher Luft, Maureen E. Callow, James A. Callow, and Joseph M. DeSimone
Langmuir 2011 Volume 27(Issue 17) pp:10365-10369
Publication Date(Web):August 9, 2011
DOI:10.1021/la202427z
Herein we report the design of a photocurable amphiphilic co-network consisting of perfluoropolyether and poly(ethylene glycol) segments that display outstanding nonfouling characteristics with respect to spores of green fouling alga Ulva when cured under high humidity conditions. The analysis of contact angle hysteresis revealed that the poly(ethylene glycol) density at the surface was enhanced when cured under high humidity. The nonfouling behavior of nonbiocidal surfaces against marine fouling is rare because such surfaces usually reduce the adhesion of organisms rather than inhibit colonization. We propose that the resultant surface segregation of these materials induced by high humidity may be a promising strategy for achieving nonfouling materials, and such an approach is more important than simply concentrating poly(ethylene glycol) moieties at an interface because the low surface energy has been maintained in our work.
Co-reporter:Yapei Wang, Timothy J. Merkel, Kai Chen, Catherine Ann Fromen, Douglas E. Betts, and Joseph M. DeSimone
Langmuir 2011 Volume 27(Issue 2) pp:524-528
Publication Date(Web):December 17, 2010
DOI:10.1021/la1045095
Herein we describe a versatile and readily scalable approach for the fabrication of particles with a variety of shapes and sizes from a single master template by augmenting the particle replication in nonwetting templates (PRINT) method with mechanical elongation. Repetition of the elongation steps in one direction leads to the fabrication of linear particles with high aspect ratio (AR), over 40 times greater than in the original master, while a range of particle shapes can be obtained by repeating the elongation procedure while changing the stretching direction, generating diamond, rectangular, curved parallelogram particles from a single cubic master.
Co-reporter:Yapei Wang, Douglas E. Betts, John A. Finlay, Lenora Brewer, Maureen E. Callow, James A. Callow, Dean E. Wendt, and Joseph M. DeSimone
Macromolecules 2011 Volume 44(Issue 4) pp:878-885
Publication Date(Web):January 25, 2011
DOI:10.1021/ma102271t
We demonstrate a facile way of cross-linking hydrophobic perfluoropolyethers, PFPEs, with a series of hydrophilic poly(ethylene glycol)s, PEGs, to prepare a range of amphiphilic networks for use as fouling-release coatings. The PFPE matrix of the networks endows the coating with a low surface energy while the PEG is added to weaken fouling adhesion. It is therefore envisioned that the coating surfaces of these optically transparent and mechanically robust films will display hydrophobicity leading to nonfouling and fouling release characteristics. Two kinds of functionalized PEG oligomers have been cross-linked with reactive, dimethacryloxy-functionalized PFPE oligomers to form a range of amphiphilic networks: (i) a monomethacryloxy-functionalized PEG macromonomer (454 g/mol) (PEG454−MA) which was used to yield blends with flexible PEG chains on the surface as well as in bulk and (ii) a dimethacryloxy-functionalized PEG (550 g/mol) (PEG550−DMA) which results in PEG chains that are relatively more restricted in the network blends and serve as an added difunctional cross-linker for the network along with the dimethacryloxy-functionalized PFPE. The PFPE/PEG cross-linked networks coated on a substrate show very low swelling characteristics in water when PEG454−MA comprises not more than 10 wt % of the overall composition or when PEG550−DMA is used and does not comprise more than 30 wt % of the overall composition. The PFPE/PEG454−MA coatings having PEG chains with one untethered chain end were found to display relatively high spore and barnacle release performance in comparison to PFPE/PEG550−DMA coatings which have the PEG chains in a more restricted network topology.
Co-reporter:Timothy J. Merkel
Science Translational Medicine 2011 Vol 3(73) pp:73ps8
Publication Date(Web):09 Mar 2011
DOI:10.1126/scitranslmed.3002137
Nanodiamond-drug conjugates show antitumor activity in mouse models of chemoresistant breast and liver cancer.
Co-reporter:Timothy J. Merkel;Stephen W. Jones;Farrell R. Kersey;J. Christopher Luft;Andrew Z. Wang;Adam R. Shields;Kevin P. Herlihy;Mary Napier;Huali Wu;William C. Zamboni;James E. Bear
PNAS 2011 Volume 108 (Issue 2 ) pp:586-591
Publication Date(Web):2011-01-11
DOI:10.1073/pnas.1010013108
It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells
in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity
in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing
the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the
lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of
conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination
phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.
Co-reporter:Stuart S. Williams, Scott Retterer, Rene Lopez, Ricardo Ruiz, Edward T. Samulski and Joseph M. DeSimone
Nano Letters 2010 Volume 10(Issue 4) pp:1421-1428
Publication Date(Web):February 23, 2010
DOI:10.1021/nl100326q
Several perfluoropolyether (PFPE)-based elastomers for high-resolution replica molding applications are explored. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface tension values (<25 mN/m). Using large area (>4 in.2) master templates, we experimentally show the relationship between mold resolution and material properties such as modulus and surface tension for materials used in this study. A composite mold approach was used to form flexible molds out of stiff, high modulus materials that allow for replication of sub-20 nm post structures. Sub-100 nm line grating master templates, formed using e-beam lithography, were used to determine the experimental stability of the molding materials. It was observed that as the feature spacing decreased, high modulus PFPE tetramethacrylate (TMA) composite molds were able to effectively replicate the nanograting structures without cracking or tear-out defects that typically occur with high modulus elastomers.
Co-reporter:Janine Nunes, Kevin P. Herlihy, Lamar Mair, Richard Superfine and Joseph M. DeSimone
Nano Letters 2010 Volume 10(Issue 4) pp:1113-1119
Publication Date(Web):March 24, 2010
DOI:10.1021/nl904152e
Interest in uniform multifunctional magnetic particles is driven by potential applications in biomedical and materials science. Here we demonstrate the fabrication of highly tailored nanoscale and microscale magneto-polymer composite particles using a template based approach. Regiospecific surface functionalization of the particles was performed by chemical grafting and evaporative Pt deposition. Manipulation of the particles by an applied magnetic field was demonstrated in water and hydrogen peroxide.
Co-reporter:Janine K. Nunes, Merve Ertas, Libin Du and Joseph M. DeSimone
Chemistry of Materials 2010 Volume 22(Issue 13) pp:4069
Publication Date(Web):June 15, 2010
DOI:10.1021/cm100931r
We have developed a novel composite film fabrication process that utilizes the soft lithographic approach, Particle Replication in Nonwetting Templates (PRINT). This process was found to be a very viable approach to the fabrication of well-structured, multifunctional polymer composite thin films. Particle aggregation was completely eliminated as discretely molded particles with specific shape, size and composition were maintained in well-defined arrays determined by the silicon master template. Both all-organic and polymer-ceramic composites have been generated using this technique with particle inclusions ranging in size from 200 nm to 20 μm. The composition of the composite was well-controlled with both cross-linked and thermoplastic polymeric continuous phases, as well as particle compositions ranging from cross-linked polymeric resins to the inorganic oxide, barium titanate.
Co-reporter:Zhaokang Hu, Louis M. Pitet, Marc A. Hillmyer, and Joseph M. DeSimone
Macromolecules 2010 Volume 43(Issue 24) pp:10397-10405
Publication Date(Web):November 19, 2010
DOI:10.1021/ma101180k
A new strategy has been developed to achieve durable, low surface tension fluorinated polymeric materials by copolymerizing a tetramethacryloxy-modified perfluoropolyether (PFPE) macromonomer and a fluorinated difunctional cross-linker, 1H,1H,6H,6H-perfluoro-1,6-hexyl diacrylate (PFHDA), into very highly cross-linked materials that possess a very high modulus as well as a very low surface energy. The miscibility of the two fluorinated components has been studied by measuring the cloud-point temperatures. Partially miscible mixtures yielded optically transparent samples after curing at low PFHDA contents (e.g., <40 wt %), and cloudy samples were obtained at high PFHDA contents when cured at room temperature. However, it was possible to achieve optically transparent samples with high PFHDA contents by increasing the cure temperature. The miscibility of these materials has been further studied by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and atomic force microscopy (AFM). By incorporating PFHDA into the cross-linked system, a low surface energy, very high modulus (up to 458 MPa) thermoset could be achieved which is important for many applications including as hard, abrasion-resistant coating materials.
Co-reporter:Timothy J. Merkel, Kevin P. Herlihy, Janine Nunes, Ryan M. Orgel, Jason P. Rolland and Joseph M. DeSimone
Langmuir 2010 Volume 26(Issue 16) pp:13086-13096
Publication Date(Web):December 11, 2009
DOI:10.1021/la903890h
The search for a method to fabricate nonspherical colloidal particles from a variety of materials is of growing interest. As the commercialization of nanotechnology continues to expand, the ability to translate particle-fabrication methods from a laboratory to an industrial scale is of increasing significance. In this feature article, we examine several of the most readily scalable top-down methods for the fabrication of such shape-specific particles and compare their capabilities with respect to particle composition, size, shape, and complexity as well as the scalability of the method. We offer an extensive examination of particle replication in nonwetting templates (PRINT) with regard to the versatility and scalability of this technique. We also detail the specific methods used in PRINT particle fabrication, including harvesting, purification, and surface-modification techniques, with an examination of both past and current methods.
Co-reporter:Meredith J. Hampton, Joseph L. Templeton and Joseph M. DeSimone
Langmuir 2010 Volume 26(Issue 5) pp:3012-3015
Publication Date(Web):January 26, 2010
DOI:10.1021/la904787k
Ordered, two-dimensional cadmium selenide (CdSe) arrays have been fabricated on indium-doped tin oxide (ITO) electrodes using the pattern replication in nonwetting templates (PRINT) process. CdSe quantum dots (QDs) with an average diameter of 2.7 nm and a pyridine surface ligand were used for patterning. The PRINT technique utilizes a perfluoropolyether (PFPE) elastomeric mold that is tolerant of most organic solvents, thus allowing solutions of CdSe QDs in 4-picoline to be used for patterning without significant deformation of the mold. Nanometer-scale diffraction gratings have been successfully replicated with CdSe QDs.
Co-reporter:Libin Du, Jennifer Y. Kelly, George W. Roberts, Joseph M. DeSimone
The Journal of Supercritical Fluids 2009 Volume 47(Issue 3) pp:447-457
Publication Date(Web):January 2009
DOI:10.1016/j.supflu.2008.11.011
Herein we review the environmentally friendly synthesis of fluorinated polymers in supercritical carbon dioxide (scCO2). Historically, many high-performance fluorinated materials are commercially synthesized in aqueous media using fluorinated surfactants or in non-aqueous conditions using fluorinated solvents. Our group has pioneered both the homogeneous and heterogeneous polymerization of fluorinated monomers in scCO2. This review includes discussions on the synthesis of main-chain and side-chain fluoropolymers conducted via a chain-growth or continuous process. Specific materials consist of acrylate- and styrene-based systems, poly(vinyl ether)s, tetrafluoroethylene- and vinylidenefluoride-based, as well as novel fluorinated elastomers and thermoplastics.
Co-reporter:Zhaokang Hu, John A. Finlay, Liang Chen, Douglas E. Betts, Marc A. Hillmyer, Maureen E. Callow, James A. Callow and Joseph M. DeSimone
Macromolecules 2009 Volume 42(Issue 18) pp:6999-7007
Publication Date(Web):August 28, 2009
DOI:10.1021/ma901227k
A series of reactive liquid perfluoropolyether (PFPE) precursors were synthesized which can be photochemically cross-linked (UV-cured) into high-performance PFPE elastomers in one step. To investigate how fundamental changes in the PFPE molecular structure correlate to bulk and surface properties, the variable functional end group, molecular weight, and the copolymer content were systematically explored in relation to thermal stability, contact angle/surface tension, modulus, and biofouling behavior. The morphologies of these PFPE materials were studied using differential scanning calorimetry, dynamic mechanical thermal analysis, and small-angle X-ray scattering. From these studies, it was determined that clusters of polymerized functional end groups were found to be nanophase separated within the PFPE matrix. By varying the cross-link density, the Young’s modulus of the fully cross-linked PFPE elastomeric film could be tuned from 1.5 to 90 MPa with a critical surface tension of 8.6−16 mN/m. The marine antifouling and fouling-release properties of the cross-linked PFPE elastomeric coatings were evaluated by settlement and release assays involving zoospores and sporelings (young plants), respectively, of green fouling alga Ulva.
Co-reporter:Stephanie E. A. Gratton, Stuart S. Williams, Mary E. Napier, Patrick D. Pohlhaus, Zhilian Zhou, Kenton B. Wiles, Benjamin W. Maynor, Clifton Shen, Tove Olafsen, Edward T. Samulski and Joseph M. DeSimone
Accounts of Chemical Research 2008 Volume 41(Issue 12) pp:1685
Publication Date(Web):August 23, 2008
DOI:10.1021/ar8000348
In this Account, we describe the use of perfluoropolyether (PFPE)-based materials that are able to accurately mold and replicate micro- and nanosized features using traditional techniques such as embossing as well as new techniques that we developed to exploit the exceptional surface characteristics of fluorinated substrates. Because of the unique partial wetting and nonwetting characteristics of PFPEs, we were able to go beyond the usual molding and imprint lithography approaches and have created a technique called PRINT (Particle [or Pattern] Replication In Nonwetting Templates). PRINT is a distinctive “top-down” fabrication technique capable of generating isolated particles, arrays of particles, and arrays of patterned features for a plethora of applications in both nanomedicine and materials science. A particular strength of the PRINT technology is the high-resolution molding of well-defined particles with precise control over size, shape, deformability, and surface chemistry. The level of replication obtained showcases some of the unique characteristics of PFPE molding materials. In particular, these materials arise from very low surface energy precursors with positive spreading coefficients, can be photocured at ambient temperature, and are minimally adhesive, nonswelling, and conformable. These distinctive features enable the molding of materials with unique attributes and nanometer resolution that have unprecedented scientific and technological value. For example, in nanomedicine, the use of PFPE materials with the PRINT technique allows us to design particles in which we can tailor key therapeutic parameters such as bioavailability, biodistribution, target-specific cell penetration, and controlled cargo release. Similarly, in materials science, we can fabricate optical films and lens arrays, replicate complex, naturally occurring objects such as adenovirus particles, and create 2D patterned arrays of inorganic oxides.
Co-reporter:Meredith J. Hampton;Stuart S. Williams;Zhilian Zhou;Janine Nunes;Doo-Hyun Ko;Joseph L. Templeton;Edward T. Samulski
Advanced Materials 2008 Volume 20( Issue 14) pp:2667-2673
Publication Date(Web):
DOI:10.1002/adma.200702495
Co-reporter:Stuart S. Williams, Meredith J. Hampton, Vignesh Gowrishankar, I-Kang Ding, Joseph L. Templeton, Edward T. Samulski, Joseph M. DeSimone and Michael D. McGehee
Chemistry of Materials 2008 Volume 20(Issue 16) pp:5229
Publication Date(Web):July 29, 2008
DOI:10.1021/cm800729q
We fabricated ordered bulk heterojunction photovoltaic (PV) cells using a perfluoropolyether (PFPE) elastomeric mold to control the donor−acceptor interfacial morphology within devices. Anatase titania nanostructures with postlike features ranging from 30 to 100 nm in height and 30 to 65 nm in spacing were fabricated using the Pattern Replication In Nonwetting Templates (PRINT) process. The nanostructured devices showed a 2-fold improvement in both short-circuit current (Jsc) and power conversion efficiency (PCE) relative to reference bilayer cells. Additionally, the titania was functionalized with Z907 dye to increase both the short-circuit current (Jsc) and open-circuit voltage (Voc). As a result we observed a device efficiency (ηeff) of 0.6%, the highest recorded efficiency value so far for an imprinted titania−P3HT device.
Co-reporter:Stephanie E. A. Gratton;Mary E. Napier;Patricia A. Ropp
Pharmaceutical Research 2008 Volume 25( Issue 12) pp:2845-2852
Publication Date(Web):2008 December
DOI:10.1007/s11095-008-9654-8
To investigate the cellular internalization pathways of shape- and size-specific particles as a function of zeta potential in different cell types.A top-down particle fabrication technique called PRINT was utilized to fabricate monodisperse 1 μm cylindrical particles. Cellular internalization of these PRINT particles was monitored using confocal microscopy, flow cytometry, and transmission electron microscopy. The endocytic pathway used by 1 μm cationic PRINT particles was evaluated using different inhibitory strategies. Cytotoxicity assays were used to determine the toxicity of both cationic and anionic PRINT particles in multiple cell types.Particle internalization was confirmed using confocal microscopy, flow cytometry and transmission electron microscopy. The mechanism of internalization of positively charged PRINT particles was found to be predominantly clathrin-mediated endocytosis and macropinocytosis with very few particles utilizing a caveolae-mediated endocytic pathway. The exposed charge on the surface of the particles had a significant effect on the rate of endocytosis in all cell types tested, except for the macrophage cells. No significant cytotoxicity was observed for all PRINT particles used in the present study.Cylindrical 1 μm PRINT particles were readily internalized into HeLa, NIH 3T3, OVCAR-3, MCF-7, and RAW 264.7 cells. Particles with a positive zeta potential exhibited an enhanced rate of endocytosis compared to negatively charged particles with identical sizes and shapes. It was found that PRINT particles with a positive zeta potential were endocytosed into HeLa cells using predominantely clathrin-mediated and macropinocytotic pathways.
Co-reporter:Kevin P. Herlihy, Janine Nunes and Joseph M. DeSimone
Langmuir 2008 Volume 24(Issue 16) pp:8421-8426
Publication Date(Web):July 23, 2008
DOI:10.1021/la801250g
Micrometer-sized monodisperse anisotropic polymer particles, with disk, rod, fenestrated hexagon (hexnut), and boomerang shapes, were synthesized using the particle replication in nonwetting templates (PRINT) process, and investigations were conducted on aqueous suspensions of these particles when subjected to alternating electric fields. A coplanar electrode configuration, with 1 to 2 mm electrode gaps (20−50 V ac, 0.5−5.0 kHz) was used, and the experiments were monitored with fluorescence microscopy. For all particle suspensions, the field brought about significant changes in the packing and orientation. Extensive particle chaining and packing were observed for the disk, rod, and hexnut suspensions. Because of the size and geometry of the boomerang particles, limited chaining was observed; however, the field triggered a change from random to a more ordered packing arrangement.
Co-reporter:Stephanie E.A. Gratton, Patrick D. Pohlhaus, Jin Lee, Ji Guo, Moo J. Cho, Joseph M. DeSimone
Journal of Controlled Release 2007 Volume 121(1–2) pp:10-18
Publication Date(Web):16 August 2007
DOI:10.1016/j.jconrel.2007.05.027
A novel method for the fabrication of polymeric particles on the order of tens of nanometers to several microns is described. This imprint lithographic technique called PRINT™ (Particle Replication In Non-wetting Templates), takes advantage of the unique properties of elastomeric molds comprised of a low surface energy perfluoropolyether network, allowing the production of monodisperse, shape-specific nanoparticles from an extensive array of organic precursors. This engineered nature of particle production has a number of advantages over the construction of traditional nanoparticles such as liposomes, dendrimers, and colloidal precipitates. The gentle “top down” approach of PRINT enables the simultaneous and independent control over particle size and shape, composition, and surface functionality, and permits the loading of delicate cargos such as small organic therapeutics and biological macromolecules. Thus, this single tool serves as a comprehensive platform for the rational design and investigation of new nanocarriers in medicine, having applications ranging from therapeutics to advanced diagnostics. Preliminary in vitro and in vivo studies were conducted, demonstrating the future utility of PRINT particles as delivery vectors in nanomedicine. Monodisperse 200 nm poly(ethylene glycol)-based (PEG) particles were fabricated using PRINT methodology and characterized via scanning electron microscopy and dynamic light scattering. Incubation with HeLa cells showed very little cytotoxicity, even at high concentrations. The biodistribution and pharmacokinetics of [125I]-labeled particles were studied in healthy mice following bolus tail vein administration. The particles were distributed mainly to the liver and the spleen with an apparent distribution t1/2 of approximately 17 min followed by slow redistribution with a t1/2 of 3.3 h. The volume of distribution for the central and peripheral compartments was found to be approximately 3 mL and 5 mL, respectively.
Co-reporter:Colin D. Wood, Udo Michel, Jason P. Rolland, Joseph M. DeSimone
Journal of Fluorine Chemistry 2004 Volume 125(Issue 11) pp:1671-1676
Publication Date(Web):November 2004
DOI:10.1016/j.jfluchem.2004.09.029
We report the synthesis of two classes of fluoropolymers that could impact several key lithographic techniques; one has potential applications in next generation photolithography (193 nm, 157 nm, and immersion lithography) and the other in lithographic techniques which are emerging as viable alternatives to photolithography for future applications (i.e., soft lithography).A solvent resistant photocurable “liquid Teflon” which can be used for microfluidic device fabrication, actuation of the valve is shown.
Co-reporter:Stephen M. Gross;W. Clayton Bunyard;Karen Erford;George W. Roberts;Douglas J. Kiserow
Journal of Polymer Science Part A: Polymer Chemistry 2002 Volume 40(Issue 1) pp:171-178
Publication Date(Web):20 NOV 2001
DOI:10.1002/pola.10098
Despite the industrial significance of poly(bisphenol A carbonate), there is a scarcity of open literature on the equilibrium of the melt-phase process. In fact, the equilibrium constant (Keq) for this reaction has never been measured directly. This article describes a process on the basis of NMR for the measurement of Keq for the reaction between bisphenol A and diphenyl carbonate in the presence and absence of a catalyst. The apparent enthalpy and entropy were calculated using a van't Hoff plot. Decomposition of bisphenol A is a common side reaction in the melt-phase reaction performed at high temperatures in the presence of catalyst. The effect of these side reactions on the Keq in the presence of catalyst is determined. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 171–178, 2002
Co-reporter:Sharon Wells;Weijun Ye
Journal of Polymer Science Part A: Polymer Chemistry 2001 Volume 39(Issue 21) pp:3841-3849
Publication Date(Web):27 SEP 2001
DOI:10.1002/pola.10018
Well-defined D-glucose-containing glycopolymers, poly(3-O-methacryloyl-1,2 : 5,6-di-O-isopropylidene-D-glucofuranose) (PMAIpGlc), and diblock copolymers of PMAIpGlc with poly(1,1-dihydroperfluorooctyl methacrylate) (PFOMA) were synthesized by living anionic polymerization in THF at −78 °C with 1,1-diphenylhexyllithium in the presence of lithium chloride. The resulting polymers were found to possess predictable molecular weights and very narrow molecular weight distributions (MWD, Mw/Mn ≤ 1.16). Removal of the acetal protective groups from the protected glycopolymer block copolymer was carried out using 90% trifluoroacetic acid at room temperature, yielding a hydrophilic block copolymer with pendant glucose moieties. Both protected (lipophilic/CO2-philic) and deprotected (hydrophilic/CO2-philic) fluorocopolymers were proved to be CO2 amphiphiles. Their solubility in CO2 was heavily influenced by the amphiphilic structure, such as the copolymer compositions and the polarities of sugar block. Light-scattering studies showed that, after removal of the protective groups, the deprotected block copolymer formed aggregate structures in liquid CO2 with an average micellar size of 27 nm. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3841–3849, 2001
Co-reporter:Sharon L. Wells
Angewandte Chemie 2001 Volume 113(Issue 3) pp:
Publication Date(Web):30 JAN 2001
DOI:10.1002/1521-3757(20010202)113:3<534::AID-ANGE534>3.0.CO;2-R
Komprimiert zu einer Flüssigkeit oder einem überkritischen Fluid ist CO2 ein gutes Lösungsmittel für viele Stoffe. Oberhalb der kritischen Temperatur und des kritischen Drucks (Tc=31.1 °C, pc=73.8 bar, siehe das CO2-Phasendiagramm in Abbildung 1) hat CO2 die Viskosität eines Gases und die Dichte einer Flüssigkeit. Dank der moderaten kritischen Bedingungen kann CO2 unter kommerziellen und sicherheitstechnischen Gesichtspunkten erfolgreich eingesetzt werden. Geringe Änderungen von Temperatur und Druck verursachen drastische Änderungen seiner Dichte, Viskosität und dielektrischen Eigenschaften. Als Lösungsmittel ist CO2 damit auf den jeweiligen Verwendungszweck gut abstimmbar und kann für zahlreiche Anwendungen maßgeschneidert eingesetzt werden. Seine einzigartigen Eigenschaften machen CO2 alles in allem zu einem Lösungsmittel der Wahl für das neue Jahrtausend. Wir wollen hier vor allem Nichtspezialisten einen allgemeinen Überblick über die derzeitigen Anwendungen von CO2 und den Stand der Technik auf diesem Gebiet geben.
Co-reporter:Joseph M DeSimone, Jason S Keiper
Current Opinion in Solid State and Materials Science 2001 Volume 5(Issue 4) pp:333-341
Publication Date(Web):August 2001
DOI:10.1016/S1359-0286(00)00041-3
Amphiphilic compounds have played a vital role in the emergence of carbon dioxide in both its liquid and supercritical states as a versatile, environmentally benign solvent. This review serves to describe recent efforts in three major areas of the field: (1) polymeric amphiphile self-assembly in carbon dioxide solutions, (2) use of surfactants as stabilizing agents for polymerizations, and (3) studies involving ‘small molecule’ surfactant assemblies in carbon dioxide.
Co-reporter:Hiroshi Shiho
Journal of Polymer Science Part A: Polymer Chemistry 2000 Volume 38(Issue 17) pp:3100-3105
Publication Date(Web):18 JUL 2000
DOI:10.1002/1099-0518(20000901)38:17<3100::AID-POLA110>3.0.CO;2-#
Radical homopolymerizations and copolymerizations of 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate (SiMA) in supercritical CO2 were investigated. The homopolymer was obtained in CO2 with a good yield. It was essentially insoluble in pure CO2 at less than 500 bar at 65 °C but was soluble in a mixture of CO2 and its monomer (10 w/v %) at 352 bar. The copolymerizations of SiMA with methyl methacrylate, 1,1-dihydroperfluorooctyl methacrylate, and styrene with various monomer feed ratios were also examined in supercritical CO2 and in bulk, and the reactivity ratios were determined. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3100–3105, 2000
Co-reporter:Hiroshi Shiho
Journal of Polymer Science Part A: Polymer Chemistry 2000 Volume 38(Issue 7) pp:1146-1153
Publication Date(Web):28 FEB 2000
DOI:10.1002/(SICI)1099-0518(20000401)38:7<1146::AID-POLA13>3.0.CO;2-8
The dispersion polymerization of styrene in supercritical CO2 utilizing CO2-philic random copolymers was investigated. The resulting high yield of polystyrene particles in the micron-size range was formed using various random copolymers as stabilizers. The particle diameter was shown to be dependent on the composition of the stabilizer, and the weight percent of the stabilizer added to the system. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1146–1153, 2000
Co-reporter:Hiroshi Shiho
Journal of Polymer Science Part A: Polymer Chemistry 2000 Volume 38(Issue 7) pp:1139-1145
Publication Date(Web):28 FEB 2000
DOI:10.1002/(SICI)1099-0518(20000401)38:7<1139::AID-POLA12>3.0.CO;2-3
Copolymerizations of 1,1-dihydroperfluorooctyl methacrylate (FOMA; M1) and methacryloxypropyl-terminated polydimethylsiloxane [M-PDMS (Mn = 5.9 K); M2] and homopolymerization of M-PDMS in supercritical CO2 are described. The homopolymerization of M-PDMS proceeded homogeneously without difficulty to produce oligomers (Mn = 30 K). The copolymerizations of FOMA and M-PDMS also proceeded homogeneously over a wide monomer feed ratio. The ratio of M-PDMS incorporated into the copolymer obtained was almost equal to the monomer feed ratio even up to the high conversion. The reactivity ratio r1 was determined to be 1.66. DSC examination of the copolymers indicated a microphase-separated morphology consisting of poly-FOMA (PFOMA) and PDMS domains for all copolymer compositions. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1139–1145, 2000
Co-reporter:A. I. Cooper,
J. D. Londono,
G. Wignall,
J. B. McClain,
E. T. Samulski,
J. S. Lin,
A. Dobrynin,
M. Rubinstein,
A. L. C. Burke,
J. M. J. Fréchet
and
J. M. DeSimone
Nature 1997 389(6649) pp:368
Publication Date(Web):
DOI:10.1038/38706
Dendrimers are well defined, highly branched polymers1, 2, 3, 4, 5 that adopt a roughly spherical, globular shape in solution. Their cores are relatively loosely packed and can trap guest molecules5, 6, 7, and by appropriate functionalization of the branch tips the macromolecules can act as unimolecular micelle-like entities6. Here we show that dendrimers with a fluorinated shell are soluble in liquid carbon dioxide and can transport CO2-insoluble molecules into this solvent within their cores. Specifically, we demonstrate the extraction of a polar ionic dye, methyl orange, from water into CO2 using these fluorinated dendrimers. This observation suggests possible uses of such macromolecules for the remediation of contaminated water, the extraction of pharmaceutical products from fermentation vessels, the selective encapsulation of drugs for targeted delivery6, 7 and the transport of reagents for chemical reactions (such as polymerization8, 9, 10, 11) in liquid and supercritical CO2 solvents.
Co-reporter:Yapei Wang, James D. Byrne, Mary E. Napier, Joseph M. DeSimone
Advanced Drug Delivery Reviews (August 2012) Volume 64(Issue 11) pp:1021-1030
Publication Date(Web):1 August 2012
DOI:10.1016/j.addr.2012.01.003
The ability to engineer particles has the potential to shift the paradigm in the creation of new medicines and diagnostics. Complete control over particle characteristics, such as size, shape, mechanical property, and surface chemistry, can enable rapid translation and facilitate the US Food and Drug Administration (FDA) approval of particle technologies for the treatment of cancer, infectious diseases, diabetes, and a host of other major illnesses. The incorporation of natural and artificial external stimuli to trigger the release of drugs enables exquisite control over the release profiles of drugs in a given environment. In this article, we examine several readily scalable top–down methods for the fabrication of shape-specific particles that utilize stimuli-responsive biomaterials for controlled drug delivery. Special attention is given to Particle Replication In Nonwetting Templates (PRINT®) technology and the application of novel triggered-release synthetic and natural polymers.Download high-res image (173KB)Download full-size image
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