In this paper, a redox-triggered drug delivery system of DOX/MSN–Au was prepared for chemo-photothermal synergistic therapy. The ultra-small gold nanoparticles (NPs) were appended to the openings of mesoporous silica nanoparticles (MSN) by Au-S bonds as the gatekeepers. Meanwhile, the gold NPs could be heated to high temperature by the near infrared (NIR) light irradiation, which is conducive to photothermal therapy. X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectrometer (FT-IR) spectra confirmed the formation of MSN-SH and MSN-Au. An in vitro NIR-induced photothermal study indicated that MSN-Au possessed concentration-dependent and power-dependent photothermal conversion capacity. Doxorubicin (DOX) was selected as the model drug loaded in the MSN. In vitro drug release showed that DOX released faster in the presence of glutathione (GSH) or NIR laser irradiation than without GSH or NIR irradiation, which suggested that the system had potentials for redox-responsive and NIR-triggered drug release. Confocal Laser Scanning Microscope (CLSM) was performed to evaluate the cellular uptake performance of DOX/MSN-Au. The cytotoxicity assay indicated that DOX/MSN-Au had a synergistic therapeutic effect by the combination of chemotherapy and photothermal therapy. This work suggested that MSN–Au could be explored as a redox-triggered drug delivery system for the chemo-photothermal synergistic therapy.Download high-res image (93KB)Download full-size image

An efficient and intelligent nano-carrier that combines cell imaging with near infrared (NIR) light and redox dual-responsive drug delivery was successfully prepared. The hollow mesoporous carbon (HMC) nanoparticles with high photothermal conversion ability were developed to increase the drug loading efficiency and realize chemotherapy and photothermal synergetic therapy. The photo-stable and luminescent carbon dots (CDs) were prepared from branched polyethyleneimine (PEI) by hydrothermal reaction. The PEI CDs (CDPEI) were grafted on the openings of HMC as the “gatekeepers” via disulfide units (HMC-SS-CDPEI) to prevent the premature release of doxorubicin (DOX). In the presence of GSH, the CDPEI separated from HMC due to the breakage of disulfide bonds, thus triggering the rapid release of the encapsulated drug. In addition, the release rate of DOX could be further accelerated by NIR light irradiation due to the increased temperature which would decrease the interaction between HMC and DOX. The fluorescence of the CDPEI is quenched when being attached to the HMC, while it is recovered when the CDPEI breaking away from HMC. Hence, the fluorescent CDPEI not only act as a gatekeeper to control drug release but also play a vital role in monitoring the process of the drug delivery. The developed HMC-SS-CDPEI showed dual-responsive drug release property and could be used as visible nano-platforms for chemo-photothermal synergistic therapy.Download high-res image (58KB)Download full-size image

In this study, we synthesized a kind of hollow mesoporous carbon (HMC) as near-infrared (NIR) nanomaterial and made a comparison between HMC and IR-820 commercially available in terms of heat generation properties and thermal stability exposed under NIR laser irradiation. The NIR-induced photothermal tests indicated that HMC had excellent heat generating capacity and remained stable after exposed to NIR laser irradiation for several times. On the contrary, the IR-820 was thermal unstable and degraded completely after exposed to NIR laser irradiation for only one time. The anticancer drug DOX was chosen as a model drug to evaluate the loading capacity and release properties of carboxylated HMC (HMC-COOH). The drug loading efficiency of HMC-COOH could reach to 39.7%. In vitro release results indicated that the release rate of DOX was markedly increased under NIR laser irradiation both in pH 5.0 and pH 7.4 PBS. Cell viability experiments indicated that HMC-COOH/DOX has a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This present research demonstrated that HMC could be employed as NIR-adsorbing agents as well as drug carriers to load lots of drug, realizing the synergistic treatment of chemotherapy and photothermal therapy.Download high-res image (331KB)Download full-size image

A distinctive and personalized nanocarrier is described here for controlled and targeted antitumor drug delivery and real-time bioimaging by combining a redox/enzyme dual-responsive disulfide-conjugated carbon dot with mesoporous silica nanoparticles (MSN-SS-CDHA). The carbon dot with controlling and targeting abilities was prepared through a polymerizing reaction by applying citric acid and HA as starting materials (named CDHA). The as-prepared MSN-SS-CDHA exhibited not only superior photostability and excellent biocompatibility, but also the ability to target A549 cells with overexpression of CD44 receptors. Upon loading the antitumor drug, doxorubicin (DOX), into the mesoporous channels of MSN nanoparticles, CDHA with a diameter size of 3 nm completely blocked the pore entrance of DOX-encapsulated MSN nanoparticles with a pore size of about 3 nm, thus preventing the premature leakage of DOX and increasing the antitumor activity until being triggered by specific stimuli in the tumor environment. The results of the cell imaging and cytotoxicity studies demonstrated that the redox/enzyme dual-responsive DOX-encapsulated MSN-SS-CDHA nanoparticles can selectively deliver and control the release of DOX into tumor cells. Ex vivo fluorescence images showed a much stronger fluorescence of MSN-SS-CDHA-DOX in the tumor site than in normal tissues, greatly facilitating the accumulation of DOX in the target tissue. However, its counterpart, MSN-SH-DOX exhibited no or much lower tumor cytotoxicity and drug accumulation in tumor tissue. In addition, MSN-SS-CD was also used as a control to investigate the ability of MSN-SS-CDHA to target A549 cells. The results obtained indicated that MSN-SS-CDHA possessed a higher cellular uptake through the CD44 receptor-mediated endocytosis compared with MSN-SS-CD in the A549 cells. Such specific redox/enzyme dual-responsive targeted nanocarriers are a useful strategy achieving selective controlled and targeted delivery of therapeutic reagents with real-time bioimaging, and may also facilitate the development of drug delivery systems for a number of clinical applications.Download high-res image (174KB)Download full-size image

•Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier.•Hyaluronic acid (HA) and PEI carbon dots (CDPEI) was grafted on HMSN via disulfide bonds.•The DOX-loaded HMSN-SS-CDPEI@HA had a high drug loading efficiency up to 30.5%.•DOX/HMSN-SS-CDPEI@HA showed redox/pH dual-responsive drug release.•DOX/HMSN-SS-CDPEI@HA showed a real-time imaging targeted drug delivery.In this work, a redox and enzyme dual-stimuli responsive drug delivery system (DDS) with tracking function (HMSN-SS-CDPEI@HA) based on carbon dots capped hollow mesoporous silica nanoparticles (HMSN) has been developed for targeted drug delivery. The positively charged CDPEI nanoparticles prepared by polyethylenimine (PEI) were grafted on the pore openings of HMSN through disulfide bonds and were used as “gatekeepers” to trap the drugs within the hollow cavity. The hyaluronic acid (HA), a natural polysaccharide, was further grafted on the surface of HMSN to realize targeted drug delivery, controlled drug release and improved the stability. Doxorubicin (DOX) was chosen as a model drug due to its wide clinical application. In vitro drug release profiles demonstrated that DOX-loaded HMSN-SS-CDPEI@HA exhibited redox and enzyme dual-responsive drug release property. In addition, the prepared HMSN-SS-CDPEI@HA exhibited excellent fluorescent properties and biocompatibility. Confocal laser scanning microscope (CLSM) and flow cytometry (FCM) illustrated that HMSN-SS-CDPEI@HA exhibited a higher cellular uptake via the CD44 receptor-mediated endocytosis by CD44-receptor over-expressed A549 cells than NIH-3T3 (receptor-negative) cells, leading to higher cytotoxicity against A549 cells than NIH 3T3 cells. This work suggested an exploration of dual-stimuli responsive as well as real-time imaging targeted drug delivery system based on HMSN and the prepared HMSN-SS-CDPEI@HA could be a promising platform for cancer therapy.Download high-res image (140KB)Download full-size image

•Poly(acrylic acid) was grafted on hollow mesoporous carbon (HMC) via disulfide bonds.•The grafted PAA could increase the biocompatibility and stability of HMC.•The DOX-loaded DOX/HMC-SS-PAA had a high drug loading efficiency up to 51.9%.•DOX/HMC-SS-PAA showed redox/pH dual-responsive and NIR-triggered drug release.•DOX/HMC-SS-PAA showed a chemo/photothermal synergistic therapy effect.In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment. The DOX loaded DOX/HMC-SS-PAA had a high drug loading amount up to 51.9%. The in vitro drug release results illustrated that DOX/HMC-SS-PAA showed redox and pH dual-responsive drug release, and the release rate could be further improved by the near infrared (NIR) irradiation. Cell viability experiment indicated that DOX/HMC-SS-PAA had a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This work suggested that HMC-SS-PAA exhibited dual-responsive drug release property and could be used as a NIR-adsorbing drug delivery system for chemo-photothermal synergistic therapy.

In this paper, a smart nanocarrier (MSNs-SS-CDPAA) is developed for redox-responsive controlled drug delivery and in vivo bioimaging by grafting fluorescent carbon dots to the surface of mesoporous silica nanoparticles (MSNs) via disulfide bonds. The polyanion polymer poly(acrylic acid) (PAA) was used to prepare the carboxyl-abundant carbon dots (CDPAA) by hydrothermal polymerization. The negatively charged CDPAA were anchored to the openings of MSNs containing the disulfide bonds through amidation and were used as gatekeepers for trapping the drugs within the pores. The in vitro release results indicated that the prepared MSNs-SS-CDPAA/DOX showed highly redox-responsive drug release in pH 7.4 and pH 5.0 PBS. In addition, the redox-responsive release mechanism was studied by measurement of the Zeta potential and fluorescence spectrophotometry. The prepared MSNs-SS-CDPAA exhibited excellent biocompatibility and fluorescence properties. Confocal laser scanning microscopy (CLSM) showed that MSNs-SS-CDPAA could emit blue, green and red fluorescence at an excitation wavelength of 408, 488 and 561 nm, respectively. In addition, MSNs-SS-CDPAA/DOX exhibited a high cellular uptake as shown by CDPAA imaging and a therapeutic effect on cancer cells by MTT assay. This study describes a novel strategy for simultaneously controlled drug delivery and real-time imaging to track the behavior of nanoparticles during tumor therapy.

•The lipid bilayer coated mesoporous silica nanocomposites (LMSNs) were successfully prepared.•The LMSNs had improved dispersing stability and uptake efficiency compared with bare mesoporous silica nanoparticles (MSNs)•The presence of the lipid bilayer could improve the biocompatibility and reliability of MSNs as drug carriers.•The prepared LMSNs can load drug with high efficiency and improve the therapeutic efficacy of the encapsulated drugs.The lipid bilayer coated mesoporous silica nanocomposites (LMSNs) were synthesized with aim to obtain better performance in the application of drug delivery. Phospholipids composed of soybean lecithin and DSPE-PEG 2000 were pre-prepared into liposomes, then they were allowed to fuse onto the mesoporous silica nanoparticles (MSNs) forming a surrounding lipid bilayer. The obtained LMSNs had an average particle size of 295 nm, zeta potential of −1.0 mV and a good dispersing stability in saline buffers. Facilitated by the affinity of the lipid bilayer with cell membrane, the internalization of LMSNs by cells was markedly increased. In addition, compared with bare MSNs, the cytotoxicity, hemolysis percentage and nonspecific BSA absorption of LMSNs were significantly reduced, making them become more reliable carriers for drug delivery. When encapsulating a model drug, doxorubicin (DOX) into LMSNs, the loading efficiency can reach as high as 16%. The obtained LMSNs-DOX exhibited a pH-responsive release behavior and the presence of the lipid bilayer did not significantly retard the release of DOX. Furthermore, LMSNs greatly enhanced the cellular accumulation and cytotoxicity of DOX toward the MCF-7 cells. In summary, the lipid bilayer coating was a simple and facile strategy to functionalize MSNs, and the obtained LMSNs exhibiting good biocompatibility were promising nanocarriers in improving the cellular uptake and therapeutic efficacy of anticancer drugs.

•Hollow mesoporous silica nanoparticles (HMSN) were used as a drug carrier.•Chitosan (CS) and PEG were grafted on the surface of HMSN via disulfide bonds.•The DOX loaded DOX/HMSN-SS-CS@PEG had a high drug loading efficiency up to 32.8%.•DOX/HMSN-SS-CS@PEG showed redox/pH dual-responsive drug release property in vitro.•The grafted PEG could increase the biocompatibility and stability of HMSN.In this paper, a hollow mesoporous silica nanoparticles (HMSN) was used as the drug vehicle to develop the redox and pH dual stimuli-responsive delivery system, in which the chitosan (CS), a biodegradable cationic polymer, was grafted on the surface of HMSN via the cleavable disulfide bonds. CS was chosen as the gatekeeper mainly due to its appropriate molecular weight as well as possessing abundant amino groups which could be protonated in the acidic condition to achieve pH-responsive drug release. In addition, the PEG was further grafted on the surface of CS to increase the stability and biocompatibility under physiological conditions. The DOX loaded DOX/HMSN-SS-CS@PEG had a relatively high drug loading efficiency up to 32.8%. In vitro release results indicated that DOX was dramatically blocked within the mesopores of HMSN-SS-CS@PEG in pH 7.4 PBS without addition of GSH. However, the release rate of DOX was markedly increased after the addition of 10 mM GSH or in pH 5.0 release medium. Moreover, the release of DOX was further improved in pH 5.0 PBS with 10 mM GSH. The HMSN-SS-CS@PEG could markedly decrease the hemolysis percent and protein adsorption, and increase the biocompatibility and stability of HMSN compared with the HMSN-SS-CS and bare HMSN. This work suggested an exploration about HMSN based stimuli-responsive drug delivery and these results demonstrated that HMSN-SS-CS@PEG exhibited dual-responsive drug release property and could be used as a promising carrier for cancer therapy.

Multidrug resistance (MDR) is known to be a great obstruction to successful chemotherapy, and considerable efforts have been devoted to reverse MDR including designing various functional drug delivery systems. In this study, hybrid lipid-capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli-responsive drug release to circumvent MDR, were specially designated for drug delivery. After modifying MSNs with hydrophobic chains through disulfide bond on the surface, lipid molecules composing polymer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to self-assemble into a surrounded lipid layer via hydrophobic interaction acting as smart valves to block the pore channels of carrier. The obtained LTMSNs had a narrow size distribution of ca. 190 nm and can be stably dispersed in body fluids, which may ensure a long circulating time and ideal enhanced permeability and retention effect. Doxorubicin (DOX) was chosen as a model drug to be encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous silica drug delivery system can achieve redox and pH-responsive release of DOX, thereby avoiding the premature leakage of drug before reaching the specific site and releasing DOX within the cancerous cells. Owing to the presence of TPGS-containing lipid layer, LTMSNs–DOX exhibited higher uptake efficiency, cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr cells compared with DOX solution, proving to be a promising vehicle to realize intracellular drug release and inhibit drug efflux.Keywords: drug delivery; lipid; mesoporous silica; multidrug resistance; polymer; stimuli-responsive release

Metastasis is the primary cause resulting in the high mortality of breast cancer. The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range of hydrophilic–lipophilic balance (HLB) including Pluronic L61, P85, P123, F127, F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The results indicated that P85 and P123 could strongly inhibit the migration and invasion of 4T1 cells. The effects of the polymers on cell healing, migration, and invasion exhibited bell-shaped dependencies on HLB of Pluronic copolymers, and the better antimetastasis effects of Pluronic copolymers could be achieved with the HLB between 8 and 16. P85 and P123 themselves could significantly inhibit pulmonary metastasis in 4T1 mammary tumor metastasis model in situ. In addition, a synergetic antimetastasis effect could be achieved during drug combination of doxorubicin hydrochloride (DOX) and P85 or P123 intravenously. The metastasis effects of P85 and P123 both in vitro and in vivo were partially attributed to the downregulation of matrix metalloproteinase-9 (MMP-9). Therefore, Pluronic copolymers with moderate HLB 8–16 such as P85 and P123 could be promising excipients with therapeutics in drug delivery systems to inhibit breast cancer metastasis.

In order to achieve efficient siRNA delivery to the brain, we designed a novel polyion complex (PIC) micelles composed of rabies virus glycoprotein (RVG) peptide tagged PEGylated polyasparthydrazide (PAHy) derivatives. The synthesized derivatives were characterized using 1H NMR. The PIC micelles were formed by electrostatic attraction between the polymer and siRNA. Then the micelles were decorated with RVG using PEG as a linker. The physiochemical properties of micelles, such as gel retardation assay, zeta potential, particle size, morphology and serum stability, were investigated. Moreover, the cytotoxicity, cellular uptake, gene silencing efficiency and in vivo distribution of micelles were also evaluated systematically. Compared with unmodified micelles, RVG-modified micelles can be more easily internalized by the neuro2a cells and efficiently silence gene expression. In vivo animal experiments further confirmed that RVG modified micelles had brain targeting ability. These results demonstrated that RVG-modified micelles were promising carriers for siRNA delivery to the brain.

•MMSN@GELs were prepared for targeted delivery of anticancer drug.•The diffusion of paclitaxel entrapped in mesopores can be retarded by gelatin shell.•The carriers guided by an external magnetic field demonstrated an improved tumor targeted efficacy.•The loaded Paclitaxel had enhanced tumor treatment efficacy and low systematic toxicity.We reported a magnetic targeted drug delivery system based on core/shell structural magnetic mesoporous silica nanoparticles (MMSNs) and the surface of MMSNs was coated by gelatin layer. In this system, the gelatin layer retarded the diffusion of paclitaxel (PTX, model drug) from quickly moving into the bulk solution to achieve sustained release of PTX. In addition, glutaraldehyde (GA) was used as crosslinking agent to crosslink the coating layer and the release of PTX could be regulated by adjusting the degree of crosslinking of the gelatin layer. The gelatin coated MMSNs (MMSN@GELs) had a saturated magnetization of 5.53 emu/g and could facilely response to an external magnet. To confirm our hypothesis that the carriers could be guided by an external magnetic field in vivo, the ex vivo imaging study and quantitative analysis were conducted. The results reflected that the external magnet altered the biodistribution of the magnetic carriers, so that more magnetic carriers were found to accumulate in tumors rather than to accumulate in normal tissues. Moreover, tumor reduction study reflected that the tumor growth of the group treated with PTX/MMSN@GELs in the presence of an external magnetic field were significantly delayed without an obvious body weight loss compared with PTX/MMSN@GELs in the absence of the magnet and with the commercial Taxol® at the same dose. All the results suggested that MMSNs coated by gelatin would be promising drug carriers for effective delivery of chemotherapeutic agents.

•Mesoporous silica nanotubes (SNT) were synthesized by using CNT as hard template, and the formation of the SNT shows that CTAB played a significant effect on the coating process.•The tube mesoporous silica materials which were seldom reported were applied in the drug delivery system to improve the loading amount and the drug dissolution.•The release rate could be controlled by the gelatin layer on the silica surface and the mechanism was illustrated.Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results.

In the past decade, mesoporous silica nanoparticles (MSNs) with a large surface area and pore volume have attracted considerable attention for their application in drug delivery and biomedicine. In this review, we highlight the recent advances in silica-assisted drug delivery systems, including (1) MSN-based immediate/sustained drug delivery systems and (2) MSN-based controlled/targeted drug delivery systems. In addition, we summarize the biomedical applications of MSNs, including (1) MSN-based biotherapeutic agent delivery; (2) MSN-assisted bioimaging applications; and (3) MSNs as bioactive materials for tissue regeneration.From the Clinical EditorThis comprehensive review presents recent advances in mesoporous silica nanoparticles assisted drug delivery systems, including both immediate and sustained delivery systems as well as controlled release and targeted drug delivery systems. In addition to achieving therapeutic agent delivery, imaging applications and potential use of silica NPs in tissue regeneration are also discussed.

•A combination of inorganic and organic materials was applied.•Mesoporous silica nanospheres (MSN) were used as drug carriers.•Chitosan and acacia were encapsulated through layer-by-layer self-assembly.•The release rate of the poorly soluble drug felodipine was effectively regulated.We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers.

A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.Keywords: 6-mercaptopurine; CD44 receptors; colloidal mesoporous silica; oligosaccharide of hyaluronic acid; redox-responsive

To meet the needs of targeted drug delivery and medical imaging, uniform mesoporous carbon spheres (UMCS) were functionalized using hyperbranched polyethyleneimine (PEI) covalently linked with fluorescein isothiocyanate (FITC) and folic acid (FA). Folate-receptor-positive KB cancer cells internalized five times more nanoparticles than A549 cells deficient in folate receptors in vitro using flow cytometry and confocal microscopy. The in vivo distribution results also confirmed that the FA–PEI–FITC–UMCS nanoparticles could target the FA-positive tumors. In addition, the specifically targeted hybrid carbon nanoparticles exhibited non-cytotoxic and controlled intracellular release (pH dependent) of the loaded agents. The in vivo antitumor effect of the paclitaxel (PTX)-loaded nanoparticles was investigated in Kunming mice harboring a hepatic H22 tumor. PTX-loaded FA–PEI–UMCS nanoparticles displayed superior antitumor effects compared to other PTX formulations, and the tumor growth inhibition rate was 86.53% compared with the control group (saline) for the enhanced targeted accumulation of NPs in tumor cells.

•The 3DOM material is customized for BSA adsorption.•The 3DOM material showed a double-plateau adsorption behavior.•The same carrier could have different release rate of adsorbed protein.•Our protein delivery systems can induce both Th1 and Th2 mediated immune response.3-D ordered macroporous (3DOM) materials were customized for BSA adsorption and further oral immunization. These carriers have a high adsorption capacity and our customized carrier showed a distinctive double-plateau adsorption behavior. Different BSA release rates (between the two plateaus) could be obtained by adjusting the ratio of the protein adsorbed on the internal surface and the external surface. This suggests that the release pattern was determined by the adsorption state. One benefit is that the same carrier could have different release profiles making it possible to study the relationship between the release behavior and adjuvant effects without any distractions. Compared with free BSA alone, a significantly higher level of serum IgG, IgA induced by BSA/3DOM was observed and the release profile had an effect on the immunity. The IgG1 and IgG2a titers suggesting that both the Th1 and Th2 mediated immune response were induced. Therefore, this research could help in the development of a novel inorganic oral adjuvant and provide a new avenue for the administration of oral vaccine.

In this work, a peptide derived from the rabies virus glycoprotein (RVG) was linked to siRNA/trimethylated chitosan (TMC) complexes through bifunctional PEG for efficient brain-targeted delivery of siRNA. The physiochemical properties of the complexes, such as siRNA complexing ability, size and ζ potential, morphology, serum stability, and cytotoxicity, were investigated prior to studying the cellular uptake, in vitro gene silencing efficiency, and in vivo biodistribution. The RVG-peptide-linked siRNA/TMC–PEG complexes showed increased serum stability, negligible cytotoxicity, and higher cellular uptake than the unmodified siRNA/TMC–mPEG complexes in acetylcholine receptor positive Neuro2a cells. The potent knockdown of BACE1, a therapeutic target in Alzheimer’s disease, demonstrated the gene silencing efficiency. In vivo imaging analysis showed significant accumulation of Cy5–siRNA in the isolated brain of mice injected with RVG-peptide-linked complexes. Therefore, the RVG-peptide-linked TMC–PEG developed in this study can be used as a potential carrier for delivery of siRNA to the brain.

•Exploitation of 3D cubic mesoporous silica (16 nm) as a carrier was completed.•The release rate of CEL increased on increasing the pore size of carriers.•The crystallinity of CEL can be changed by 3D face-centered cubic pore structure.•3D cubic mesoporous silica (up to over 10 nm) shows superior release properties.The purposes of the present work were to explore the potential application of 3D face-centered cubic mesoporous silica (FMS) with pore size of 16.0 nm as a delivery system for poorly soluble drugs and investigate the effect of pore size on the dissolution rate. FMS with different pore sizes (16.0, 6.9 and 3.7 nm) was successfully synthesized by using Pluronic block co-polymer F127 as a template and adjusting the reaction temperatures. Celecoxib (CEL), which is a BCS class II drug, was used as a model drug and loaded into FMS with different pore sizes by the solvent deposition method at a drug–silica ratio of 1:4. Characterization using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transformation infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), nitrogen adsorption, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) was used to systematically investigate the drug loading process.The results obtained showed that CEL was in a non-crystalline state after incorporation of CEL into the pores of FMS-15 with pore size of 16.0 nm. In vitro dissolution was carried out to demonstrate the effects of FMS with different pore sizes on the release of CEL. The results obtained indicated that the dissolution rate of CEL from FMS-15 was significantly enhanced compared with pure CEL. This could be explained by supposing that CEL encountered less diffusion resistance and its crystallinity decreased due to the large pore size of 16.0 nm and the nanopore channels of FMS-15. Moreover, drug loading and pore size both play an important role in enhancing the dissolution properties for the poorly water-soluble drugs. As the pore size between 3.7 and 16.0 nm increased, the dissolution rate of CEL from FMS gradually increased.

•Uniform-sized PLGA–lipid lipospheres for oral delivery of proteins were produced by premix membrane emulsification combined with double-emulsion method.•The protein structure was effectively maintained during the preparation.•Lipospheres achieved higher loading capacity, entrapment efficiency and lower initial burst for loaded proteins than PLGA microspheres.•Lipospheres showed high transcytotic efficiency via M cell model, indicating a potential enhancement of intestinal absorption for entrapped proteins.•The PLGA–lipid liposphere could be a promising platform for enhancing the proteins oral bioavailability.The main challenge in the oral delivery of protein drugs is to enhance their oral bioavailability. Herein, we report the uniform-sized liposphere prepared by premix membrane emulsification combined with W1/O/W2 double-emulsion method as a potential oral carrier for proteins. The protein-loaded liposphere was composed of a hydrophobic poly (d, l-lactide-co-glycolide) (PLGA) core and the lipid molecules self-assembled at the interface of W1/O and O/W2. During the preparation, the protein structure was effectively maintained. Compared with PLGA microsphere, the liposphere achieved a higher loading capacity (LC, 20.18%), entrapment efficiency (EE, 90.82%) and a lower initial burst (24.73%). Importantly, the lipospheres also showed high transcytotic efficiency with human microfold cell (M cell) model, leading to a potential enhancement of intestinal absorption. This result, together with the above studies supported that the PLGA–lipid liposphere could be a promising platform for enhancing the proteins oral bioavailability.

•Mesoporous carbon with spherical pore structure was prepared according to the needlelike crystalline of celecoxib.•The crystalline of CEL could be controlled by MC using different drug loading methods.•The crystallinity of CEL is reduced when increasing the amounts of drug loading.The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability.

A novel spherical nanosilica matrix (SNM) together with chitosan (CTS) encapsulated SNM (CTS-SNM) was developed in order to investigate the feasibility of using chitosan to regulate drug release rate from porous silica and obtain an oral sustained drug delivery system. To achieve this goal, we synthesized a spherical nanosilica matrix (SNM) and incorporated chitosan chains on the SNM surface. Solvent evaporation method was adopted to load the model drug carvedilol into SNM and CTS-SNM. The physicochemical properties of the drug carriers and drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The structural changes in CTS-SNM in simulated gastrointestinal fluid as well as the relationships between swelling effect of chitosan and in vitro drug release behaviors were investigated. Pharmacokinetic and bioavailability aspects were also discussed. The results showed that the powerful dispersing effect of SNM and the blocking action due to the swelling of chitosan were the two main factors contributing to the sustained drug release behavior. The swelling effect of chitosan in an acidic environment together with the shrinking effect in a relatively alkaline environment allowed regulation of drug release behavior in simulated gastrointestinal fluid. An in vivo study showed that the bioavailability of CAR was improved 182% compared with that of the commercial capsule when SNM was used as the drug carrier. As for CAR-CTS-SNM, the Tmax of CAR was delayed by about 3.4 h and the bioavailability was slightly increased in comparison with the commercial capsule. We believe that SNM and CTS-SNM developed in this study will help increase the use of polymers and inorganic materials in pharmaceutical applications and stimulate the design of oral drug delivery systems for immediate or sustained release of poorly water-soluble drugs.Keywords: carvedilol; chitosan; drug delivery; nanosilica matrix; poorly water-soluble drug; sustained release;

Cotton-like amorphous mesoporous titania (APMT) nanoparticles with 3-D netlike pores were synthesized by a simple and reproducible method and the potential of APMT as a carrier for poorly water-soluble drugs was explored. In order to study the effect of different crystal forms of titania on drug loading and release behaviors, a novel anatase mesoporous titania (ATMT) was also prepared through a facile method using pluronic F127 as a template and titanium(IV) isopropoxide (TIP) as a titania source. The model drug carvedilol (CAR) was effectively loaded into the pores of APMT and ATMT through solvent deposition method, according to results of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In compared with ATMT, APMT showed a more rapid release profile, which may be attribute to the netlike pores, small pore size (2–3 nm) as well as absorbed water and hydrate water on the surface, based on results of X-ray diffraction (XRD), N2 adsorption/desorption, SEM/TEM and in vitro dissolution test. Definitely, the results confirmed that the drug loading and release behaviors were heavily dependent on the crystal forms of the carriers, which will provide a new thread for formulation of poorly water-soluble drugs.Graphical abstractHighlights► Simple synthesis of amorphous mesoporous TiO2 nanospheres with 3-D netlike pores. ► The feasibility of amorphous mesoporous TiO2 nanospheres as drug vehicles. ► The improved delivery of drugs by mesoporous TiO2. ► The establishment of relationship between the crystal forms of carriers and drug delivery property.

The present work was proposed not only to exploit the potential of 3D cage-like mesoporous silica SBA-16 with a well-defined spherical morphology as a carrier for poorly soluble drugs, but also to compare the drug loading and release properties of 3D cubic SBA-16 with that of classic 2D hexagonal MCM-41. SBA-16 microsphere with highly ordered mesostructures was synthesized by a facile method using block co-polymer F127 as template, cetyltrimethylammonium bromide (CTAB) as co-template and tetraethyl orthosilicate (TEOS) as silica source. Carvedilol (CAR), an antihypertensive agent, was used as a model drug and loaded into mesoporous silica via solvent deposition method at drug–silica ratio of 1:3. In vitro dissolution was performed in both simulated intestinal fluid (SIF, pH 6.8) and simulated gastric fluid (SGF, pH 1.2). Of particular interest was that in SIF both MCM-41 and SBA-16 samples exhibited promoted dissolution profile for CAR as compared to its corresponding crystalline form which exhibited poor dissolution behavior. This dissolution-enhancing effect might be due to the non-crystalline state and increased surface area of confined CAR as well as the hydrophilic nature of silica. In comparison with MCM-41, SBA-16 displayed a more rapid release profile in both SIF and SGF, which may be ascribed to the 3D interconnected pore networks and the highly accessible surface areas. The suitability of the utilization of SBA-16 microsphere as carriers will open new avenues for the formulation of poorly soluble drugs.Graphical abstractHighlights► Simplified synthesis of 3D cubic SBA-16 with well-defined spherical morphology. ► The feasibility of the produced SBA-16 microspheres as drug vehicles. ► Comparison between SBA-16 and classic 2D channel-like MCM-41 for drug delivery. ► The improved delivery of carvedilol by mesoporous materials.

The main aim of this study was to prepare nanosized hydroxycarbonate apatite (HCA) as a drug carrier to improve the dissolution rate and increase the bioavailability of poorly soluble drugs, intended to be administered orally. In the present study, uniform mesoporous HCA nanoparticles were synthesized using CaCO3 as a sacrificial template by the hydrothermal method in the presence of cetyltrimethylammonium bromide (CTAB) as a surfactant. The prepared HCA was used as a drug carrier to investigate the drug uptake and release properties employing carvedilol (CAR) as a model drug. The structure and morphology of mesoporous HCA, and the successful storage/release of CAR were systematically studied by N2 adsorption, scanning electron microscopy (SEM), powder X-Ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, Fourier transform infrared (FT-IR) spectroscopy, and UV–VIS spectrophotometry. In vitro drug dissolution tests showed that mesoporous HCA produced burst release of CAR in comparison with micronized CAR in simulated gastric fluid and intestinal fluid. Stability test result indicated that amorphous state of CAR loaded in HCA nanoparticles had a good physical stability after room storage for 6 months. Hence, mesoporous HCA nanoparticles are excellent drug carriers for the oral delivery of poorly soluble drugs.Highlights► Mesoporous hydroxycarbonate (HCA) was synthesized using CaCO3 as a template. ► Poorly water-soluble drug carvedilol was selected as a model drug. ► Carvedilol loaded in mesoporous HCA was in an amorphous state. ► Mesoporous HCA had high drug load efficiency and provided fast release of carvedilol. ► HCA is a good carrier for the oral delivery of poorly water-soluble drugs.

A facile and simplified method was developed for the synthesis of 3D cubic mesoporous SBA-16 with both a spherical morphology and controllable pore size. The addition of CTAB during the synthesis allowed not only good control over the macroscopic morphology but also a significant reduction in the synthesis time. Notably, the pore size can simultaneously be adjusted by simply controlling the heating temperature. The pharmaceutical performance of the resulting SBA-16 for the delivery of the water-insoluble drug indomethacin (IMC), a non-steroidal anti-inflammatory agent used as a model drug, was systematically studied using nitrogen adsorption, powder X-ray diffraction, differential scanning calorimetry, infrared spectrometry and in vitro dissolution investigations. It was found that IMC could be effectively loaded into mesoporous SBA-16 via the solvent deposition method. An altered physical state and a marked improvement in the dissolution rate were observed for IMC after being loaded into SBA-16 microspheres. In particular, SBA-16 microspheres with the largest pore size (9.0 nm) and highly open and accessible pore networks exhibited the fastest drug release profile. We envisage that the improved drug delivery profiles obtained using SBA-16 as described in our work will offer an interesting option for the formulation of poorly water-soluble drugs.Graphical abstractA facile and simplified method was developed for the synthesis of 3D cubic mesoporous SBA-16 with both a spherical morphology and controllable pore size.Highlights► Simple synthesis of 3D cubic SBA-16 microspheres with a controllable pore size. ► The suitability of the produced SBA-16 microspheres as drug vehicles. ► The improved delivery of water-insoluble drugs by mesoporous materials. ► The establishment of relationship between the pore size and drug delivery property.

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol−1 from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

In this study, a polymeric lipid nanoparticle (NP) (simplified as Lipid NP) was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide) (PLGA) core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA) was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC) and entrapment efficiency (EE) for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI) environment for a long time. In addition, a human microfold cell (M-cell) transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.

In the current study, mesoporous carbon (MC) with pore volume (1.53 cm3/g) and pore size (9.74 nm) was successfully prepared as a carrier for celecoxib (CEL). Celecoxib was loaded into the pore channels of MC using three different methods: solvent evaporation method, absorption method and physical mixing method. Solid-state characterization methods, such as SEM, TEM, BET, DSC and XRD were used to systematically investigate the process of the drug loading system. Dissolution tests were performed to examine the effects of MC on the release of CEL. Furthermore, the cytotoxicity, wound healing, migration and invasion experiments were carried out to measure the contribution of MC to the anti-tumor metastasis ability of celecoxib on MDA-MB-231 cells. The results showed that CEL could be kept in a non-crystalline state when they were incorporated into the MC using the solvent evaporation method or absorption method. The dissolution rate of CEL released from MCS (Mesoporous carbon – Celecoxib – Solvent evaporation method) and MCA (Mesoporous carbon – Celecoxib – Absorption evaporation method) was all significantly higher than that of pure CEL. The cumulative release for MCS within the 5 min was up to 51.86%. MCS enhanced the inhibitory effect of CEL on the migration and invasion of MDA-MB-231 cells.

Hybrid mesoporous silica nanoparticles (MSNs) modified with polymer polyethylene glycol (PEG) through the biodegradable disulfide bonds were prepared to achieve ‘on demand’ drug release. In this system, PEG chains were chosen as the representative gatekeepers that can block drugs within the mesopores of MSNs. After the addition of glutathione (GSH), the gatekeepers were removed from the pore outlets of MSNs, followed by the release of encapsulated drugs. In this research, the effects of grafting density of gatekeepers on the drug release and biocompatibility of silica carriers were also investigated. First, PEG modified MSNs were prepared by the condensation reaction between the carboxyl groups of MSN and the hydroxyl of PEG. The structure of the resultant MSN-SS-PEG was characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption isotherms analysis and Fourier transform infrared spectroscopy (FTIR). Rhodamine B (RhB) as the model drug was loaded into MSNs. The in vitro assay results indicated that RhB was released rapidly after the addition of 10 mM GSH; M1-SS-PEG had the best capping efficiency compared with M0.5 and M1.5 groups. Moreover, hemolysis assay, serum protein adsorption and cell viability test indicated that with the increase of PEG grafting density, the biocompatibility of silica carriers increased.Download high-res image (169KB)Download full-size image

•Hollow mesoporous silica was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive.•Hollow mesoporous silica preformed as a high drug loading carrier for regulation insoluble drug release, which can achieve sustained release.•The difference between normal mesoporous silica (NMS) and HMS in drug loading efficiency, drug release behavior and solid state were also studied systematically.The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What’ more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system and pharmaceutic adjuvant.Download high-res image (134KB)Download full-size image

In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro, the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808 nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy.Figure optionsDownload full-size imageDownload high-quality image (67 K)Download as PowerPoint slide

Fibrous ordered mesoporous carbon (FOMC) was developed as a new drug delivery system for loading an insoluble drug, designed to be orally administered, and then to enhance the drug loading capacity, improve the dissolution rate, enhance the oral bioavailability and reduce the gastric damage. Celecoxib (CEL) was chosen as a model drug. The nanostructures and effect of different pore sizes (4.4–7.0 nm) on drug loading and release properties were studied. The results showed that FOMC has a high drug loading capacity (0.599 g/g, drug weight/carrier weight) and the dissolution rate of CEL from FOMC was much faster than pure crystalline CEL using buffer (pH 6.8) as a dissolution medium. Moreover, the oral bioavailability of CEL loaded into FOMC was significantly improved compared with that of CEL capsules and the gastric damage caused by CEL which was loaded in FOMC was also reduced, demonstrating the protective effect of FOMC.Download high-res image (93KB)Download full-size image