Co-reporter:Jing Lu, Yi Zhao, Xiaoju Zhou, Jian Hua He, Yun Yang, Cuiping Jiang, Zitong Qi, Wenli Zhang, and Jianping Liu
Biomacromolecules August 14, 2017 Volume 18(Issue 8) pp:2286-2286
Publication Date(Web):July 24, 2017
DOI:10.1021/acs.biomac.7b00436
A biofunctional polymer–lipid hybrid high-density lipoprotein-mimicking nanoparticle (HNP) loading anti-miR155 was constructed for combined antiatherogenic effects on macrophages. The HNP consisted of an anti-miR155 core condensed by acid-labile polyethylenimine (acid-labile PEI) polymers and a lipid bilayer coat that was decorated with apolipoprotein A-1, termed acid-labile PEI/HNP. The acid-labile PEI was synthesized with low-molecular-weight PEI and glutaraldehyde to reduce the cytotoxicity and facilitate nucleic acids escaping from acidic endolysosomes. The increased silencing efficiency of acid-labile PEI/HNP was ascribed to the clathrin-mediated endocytosis and successful endolysosomal escape. Decreased intracellular reactive oxygen species production and DiI-oxLDL uptake revealed the antioxidant activities of both anti-miR155 and HNP. Cholesterol efflux assay indicated the potential of HNP in reverse cholesterol transport. Collectively, the acid-labile PEI/HNP not only realized the efficacy of anti-miR155 in macrophages but also exerted the antiatherosclerotic biofunction of HNP.
Co-reporter:Cuiping Jiang, Yi Zhao, Yun Yang, Mengyuan Zhang, Jianhua He, Jing Lu, Wenli Zhang, Jianping Liu
Journal of Controlled Release 2017 Volume 259(Volume 259) pp:
Publication Date(Web):10 August 2017
DOI:10.1016/j.jconrel.2017.03.073
Co-reporter:Yi Zhao, Cuiping Jiang, Jianhua He, Qing Guo, Jing Lu, Yun Yang, Wenli Zhang, and Jianping Liu
Bioconjugate Chemistry 2017 Volume 28(Issue 2) pp:
Publication Date(Web):December 22, 2016
DOI:10.1021/acs.bioconjchem.6b00600
An atorvastatin calcium (AT)-loaded dextran sulfate (DXS)-coated core–shell reconstituted high density lipoprotein (rHDL), termed AT-DXS-LP-rHDL, was developed for targeted drug delivery to macrophages and suppression of inflammation via the high affinity of DXS with scavenge receptor class AI (SR-AI) as well as depletion of intracellular cholesterol by apolipoprotein A-I (apoA-I)-mediated cholesterol efflux. These core–shell nanoparticles comprising an AT-loaded negatively charged poly(lactide-co-glycolide) (PLGA) core and a cationic lipid bilayer shell were prepared by nanoprecipitation method followed by thin film hydration and extrusion. The nanoparticles were further functionalized with apoA-I and DXS via sodium cholate mediation and electrostatic interaction, respectively. The core–shell structure and the surface coating of apoA-I and DXS were verified by the increased particle size, inverted zeta potential, and reduced in vitro drug release rate. The TEM image further confirmed the entrapment of the PLGA nanoparticles in the aqueous interior of the liposomes. In vitro cell viability assay showed the biocompatibility of the AT-loaded nanocarriers. The cellular uptake study illustrated that the targeting efficacy to macrophages increased in the following order: PLGA nanoparticles (P-NP), core–shell nanoparticles (LP-NP), core–shell rHDL (LP-rHDL), and DXS-LP-rHDL. Moreover, cellular drug efficacy of AT-loaded nanoparticles in preventing macrophage-derived foam cell formation and inflammation such as intracellular lipid deposition, cholesterol esters content, DiI-oxLDL uptake, cholesterol efflux, and secretion of TNF-α, IL-6, and IL-10 was much better than that of the drug-free nanoparticles, consistent with the results of cellular uptake study. Collectively, AT-DXS-LP-rHDL, as multifunctional carriers, could not only deliver more drug to macrophages, but also present antiatherogenic actions of the biofunctional nanocarriers through damping oxidized low density lipoproteins (oxLDL) uptake and promoting cholesterol efflux.
Co-reporter:Shan Lu, Pan-pan Yu, Jian-Hua He, Shuang-shuang Zhang, Yu-Long Xia, Wen-Li Zhang and Jian-Ping Liu
RSC Advances 2016 vol. 6(Issue 54) pp:49052-49059
Publication Date(Web):04 May 2016
DOI:10.1039/C6RA08392G
In order to improve the dissolution rate and oral bioavailability of lurasidone hydrochloride (LH), LH nanosuspensions (LH-NSP) were prepared by an antisolvent precipitation–ultrasonication method and characterized in this study. Three important formulation factors including the concentration of LH in the solvent, the amount of sodium dodecyl sulfonate (SDS) and poloxamer 188 (F68) in the antisolvent were optimized by the central composite design response surface methodology. Besides, the impacts of three important process parameters, namely the precipitation temperature, the power input and the duration of ultrasonication, on the particle size and polydispersity index (PDI) of LH-NSP were also investigated. The optimal values of these formulation factors were 0.21% (w/v) LH, 0.06% (w/v) SDS and 0.16% (w/v) F68, respectively, while for the process parameters, the precipitation temperature, power input and duration of ultrasonication were 5 °C, 100 W and 10 min, respectively. The particle size and PDI of the optimized LH-NSP were 124.6 ± 11.9 nm and 0.097 ± 0.0024, respectively. There was no crystalline change in the LH-NSP compared with LH raw material on the basis of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analysis results. With the reduced particle size, the solubility and in vitro dissolution rate of LH in the LH-NSP were significantly improved. Pharmacokinetic studies showed that the Cmax and AUC0–24 of the group with oral administration of the LH-NSP were both 1.5 times higher than that of raw LH.
Co-reporter:Shuangshuang Zhang, Yulong Xia, Hongxiang Yan, Ying Zhang, Wenli Zhang, Jianping Liu
Powder Technology 2016 Volume 301() pp:940-948
Publication Date(Web):November 2016
DOI:10.1016/j.powtec.2016.07.030
•Two parameters were defined to characterize the water holding ability of powder mass.•Centrifugal conditions were established to measure these two parameters.•WHAmax and WHAextrusion were additive.•The performance of powder mass in extrusion can be predicted by these parameters.The water holding ability of powder masses greatly influences their extrusion/spheronization performance during pellets preparation. To quantify this ability and explore its influence on pellets preparation, two characterized parameters were proposed. One was the maximum water content that could be retained by the mass (WHAmax), the other was the remaining water content in the mass subjected to certain extrusion force (WHAextrusion). The methods to determine WHA were established by centrifugation. MCC, κ-carrageenan, mannitol were employed to investigate the relationship between WHA and their extrusion/spheronization performance. The results showed that the WHAmax and WHAextrusion of MCC were 1.0 g/g and 0.85 g/g, which were less than that of κ-carrageenan (WHAmax > 6.0 g/g, WHAextrusion = 3.0 g/g), accordingly. Since mannitol had the lowest parameter values (WHAmax = 0.3 g/g, WHAextrusion = 0.25 g/g), it was hard to be extruded. Therefore, κ-carrageenan (≥ 10%) or mannitol (≥ 30%) were added to prepare satisfactory pellets by increasing the WHA values (≥ 0.53 g/g) of the mixed masses. In addition, the WHA of mixed masses could be predicted based on WHA of each mass. To obtain enough extrudates and non-agglomerated pellets, the water content added in the mass should be equal with WHAmax. In conclusion, the established two parameters were useful to predict the extrusion/spheronization performance of masses, therefore, selecting the potential pelletization aids and determining the optimal water content.
Co-reporter:Shuangshuang Zhang;Ying Li;Panpan Yu;Tong Chen;Weisai Zhou
Biomedical Microdevices 2015 Volume 17( Issue 1) pp:
Publication Date(Web):2015 February
DOI:10.1007/s10544-014-9924-7
The release of cupric ion from copper intrauterine device (Cu-IUD) in human uterus is essential for contraception. However, excessive cupric ion will cause cytotoxic effect. In this paper, we investigated the influence of device characteristics (frame, copper surface area, shape, copper type and indomethacin) on copper release for the efficacy and adverse effects vary with IUD types which may correlate to their different release behaviors. Nine types of Cu-IUDs were selected and incubated in simulated uterine fluid. They were paired for comparison based on the device properties and the release of cupric ion was determined by flame atomic absorption spectrometer for about 160 days. The result showed that there was a burst release during the first month and the release rate tends to slow down and become steady afterwards. In addition, the copper release was mainly influenced by frame, indomethacin and copper type (copper wire and copper sleeve) while the shape variation had little effect on copper release throughout the experiment. Moreover, the influence of copper surface area was only noticeable during the first month. These findings were seldom reported before and may provide some useful information for the design of Cu-IUDs.
Co-reporter:Lisha Liu, Hongliang He, Mengyuan Zhang, Shuangshuang Zhang, Wenli Zhang, Jianping Liu
Biomaterials 2014 35(27) pp: 8002-8014
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.05.081
Co-reporter:Hongliang He;Lisha Liu;Hui Bai;Ji Wang;Yan Zhang
Pharmaceutical Research 2014 Volume 31( Issue 7) pp:1689-1709
Publication Date(Web):2014 July
DOI:10.1007/s11095-013-1273-3
Our previous studies indicated that drug leaked from discoidal reconstituted high density lipoprotein (d-rHDL) during the remodeling behaviors induced by lecithin cholesterol acyl transferase (LCAT) abundant in circulation, thus decreasing the drug amount delivered into the target. In this study, arachidonic acid (AA)-modified d-rHDL loaded with lovastatin (LT) were engineered as AA-LT-d-rHDL to explore whether AA modification could reduce the drug leakage during the remodeling behaviors induced by LCAT and further deliver more drug into target cells to improve efficacy.After successful preparation of AA-LT-d-rHDL with different AA modification amount, a series of in vitro remodeling behaviors were investigated. Furthermore, inhibition on macrophage-derived foam cell formation was chosen to evaluate drug efficacy of AA-LT-d-rHDL.In vitro physicochemical characterizations studies showed that all LT-d-rHDL and AA-LT-d-rHDL preparations had nano-size, negative surface charge, high entrapment efficiency (EE) and comparable drug loading efficiency (DL). With increment of AA modification amount, AA-LT-d-rHDL manifested lower reactivity with LCAT, thus significantly reducing the undesired drug leakage during the remodeling behaviors induced by LCAT, eventually exerting stronger efficacy on inhibition of macrophage-derived foam cell formation.AA-LT-d-rHDL could decrease the drug leakage during the remodeling behaviors induced by LCAT and fulfill efficient drug delivery.
Co-reporter:Wenli Zhang, Hongliang He, Jianping Liu, Ji Wang, Suyang Zhang, Shuangshuang Zhang, Zimei Wu
Biomaterials 2013 34(1) pp: 306-319
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.09.058
Co-reporter:Junting Jia;Yan Xiao;Wenli Zhang;Hongliang He;Liang Chen ;Mengyuan Zhang
Journal of Pharmaceutical Sciences 2012 Volume 101( Issue 8) pp:2900-2908
Publication Date(Web):
DOI:10.1002/jps.23210
Abstract
Discoidal recombinant high-density lipoproteins (d-rHDLs) are attractive candidates for anticancer agents because of their favorable biocompatibility, biodegradability, and receptor-mediated endocytosis. Paclitaxel (PTX)-loaded d-rHDLs (P-d-rHDLs) were prepared by thin-film dispersion/detergent dialysis methods in this study. To investigate metabolic processes that P-d-rHDLs probably encounter in circulation, influences of lecithin-cholesterol acyltransferase (LCAT) on structural and compositional changes of P-d-rHDLs were studied in vitro. The shape of P-d-rHDLs converted from discoid into sphere, particle size increased, and cholesteryl ester (CE) generated simultaneously, which were referred to as remodeling behaviors. In vitro releases tests showed that release rate of PTX from P-d-rHDLs became faster when LCAT was added to P-d-rHDLs suspensions. Human breast cancer cells' cytotoxicity and cellular uptake of P-d-rHDLs were higher than liposomes and Taxol, and decreased in the presence of LCAT. Explorations of above phenomena found that drug entrapment did not influence remodeling processes induced by LCAT, whereas there was drug leakage occurring in remodeling processes. Therefore, drug leakage resulting from remodeling processes under the action of LCAT should be paid more attentions to when using d-rHDLs as drug vehicles for anticancer drugs. This study first focuses on metabolic processes of drug carriers and elucidates them through in vitro tests. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2900–2908, 2012
Co-reporter:Pan Liu;Jin Li;Jikun Yang ;Yongqing Fan
Journal of Pharmaceutical Sciences 2012 Volume 101( Issue 8) pp:2811-2820
Publication Date(Web):
DOI:10.1002/jps.23199
Abstract
The objective of this study was to investigate the drug release mechanism and in vivo performance of Tanshinone IIA sustained-release pellets, coated with blends of polyvinyl acetate (PVAc) and poly(vinyl alcohol)–poly(ethylene glycol) (PVA–PEG) graft copolymer. A formulation screening study showed that pellets coated with PVAc–PVA–PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24h sustained release, irrespective of the coating weight (from 2% to 10%). Both the microscopic observation and mathematical model gave further insight into the underlying release mechanism, indicating that diffusion through water-filled cracks was dominant for the control of drug release. In vivo test showed that the maximum plasma concentration of sustained-release pellets was decreased from 82.13 ± 17.05 to 40.50 ± 11.72 ng mL as that of quick-release pellets. The time of maximum concentration, half time, and mean residence time were all prolonged from 3.80 ± 0.40 to 8.02 ± 0.81 h, 4.28 ± 1.21 to 8.18 ± 2.06 h, and 8.60 ± 1.59 to 17.50 ± 2.78 h, compared with uncoated preparations. A good in vitro–in vivo correlation was characterized by a high coefficient of determination (r = 0.9772). In conclusion, pellets coated with PVAc–PVA–PEG could achieve a satisfactory sustained-release behavior based on crack formation theory. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2811–2820, 2012
Co-reporter:Mengyuan Zhang, Junting Jia, Jianping Liu, Hongliang He, Lisha Liu
Asian Journal of Pharmaceutical Sciences (February 2013) Volume 8(Issue 1) pp:
Publication Date(Web):1 February 2013
DOI:10.1016/j.ajps.2013.07.002
This study is one of the first to focus on the unexpected drug leakage from discoidal recombinant high-density lipoproteins (d-rHDLs) as a consequence of remodeling process, mainly associated with lecithin-cholesterol acyltransferase (LCAT) during their metabolic process. Here, a newly monocholesterylsuccinate (CHS) modified paclitaxel-loaded d-rHDLs (cP-d-rHDLs) were constructed successfully through structural modification, thus aiming to improve the performance of d-rHDLs. And next their in vitro physiochemical properties and pharmacokinetics in Sprague–Dawley rats were elaborately investigated. Collectively our studies demonstrated that cP-d-rHDLs, whose remodeling behaviors were restrained effectively after structural modification, exhibited more excellent and promising properties as novel delivery vehicles for anti-cancer agents.
Co-reporter:Junting Jia, Yan Xiao, Jianping Liu, Wenli Zhang, ... Mengyuan Zhang
Journal of Pharmaceutical Sciences (August 2012) Volume 101(Issue 8) pp:2900-2908
Publication Date(Web):1 August 2012
DOI:10.1002/jps.23210
Discoidal recombinant high-density lipoproteins (d-rHDLs) are attractive candidates for anticancer agents because of their favorable biocompatibility, biodegradability, and receptor-mediated endocytosis. Paclitaxel (PTX)-loaded d-rHDLs (P-d-rHDLs) were prepared by thin-film dispersion/detergent dialysis methods in this study. To investigate metabolic processes that P-d-rHDLs probably encounter in circulation, influences of lecithin-cholesterol acyltransferase (LCAT) on structural and compositional changes of P-d-rHDLs were studied in vitro. The shape of P-d-rHDLs converted from discoid into sphere, particle size increased, and cholesteryl ester (CE) generated simultaneously, which were referred to as remodeling behaviors. In vitro releases tests showed that release rate of PTX from P-d-rHDLs became faster when LCAT was added to P-d-rHDLs suspensions. Human breast cancer cells' cytotoxicity and cellular uptake of P-d-rHDLs were higher than liposomes and Taxol, and decreased in the presence of LCAT. Explorations of above phenomena found that drug entrapment did not influence remodeling processes induced by LCAT, whereas there was drug leakage occurring in remodeling processes. Therefore, drug leakage resulting from remodeling processes under the action of LCAT should be paid more attentions to when using d-rHDLs as drug vehicles for anticancer drugs. This study first focuses on metabolic processes of drug carriers and elucidates them through in vitro tests.
Co-reporter:Pan Liu, Jin Li, Jianping Liu, Jikun Yang, Yongqing Fan
Journal of Pharmaceutical Sciences (August 2012) Volume 101(Issue 8) pp:2811-2820
Publication Date(Web):1 August 2012
DOI:10.1002/jps.23199
The objective of this study was to investigate the drug release mechanism and in vivo performance of Tanshinone IIA sustained-release pellets, coated with blends of polyvinyl acetate (PVAc) and poly(vinyl alcohol)–poly(ethylene glycol) (PVA–PEG) graft copolymer. A formulation screening study showed that pellets coated with PVAc–PVA–PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24h sustained release, irrespective of the coating weight (from 2% to 10%). Both the microscopic observation and mathematical model gave further insight into the underlying release mechanism, indicating that diffusion through water-filled cracks was dominant for the control of drug release. In vivo test showed that the maximum plasma concentration of sustained-release pellets was decreased from 82.13 ± 17.05 to 40.50 ± 11.72 ng mL as that of quick-release pellets. The time of maximum concentration, half time, and mean residence time were all prolonged from 3.80 ± 0.40 to 8.02 ± 0.81 h, 4.28 ± 1.21 to 8.18 ± 2.06 h, and 8.60 ± 1.59 to 17.50 ± 2.78 h, compared with uncoated preparations. A good in vitro–in vivo correlation was characterized by a high coefficient of determination (r = 0.9772). In conclusion, pellets coated with PVAc–PVA–PEG could achieve a satisfactory sustained-release behavior based on crack formation theory.