JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Jian-Bin Qiao,Qian-Qian Fan,Lei Xing,Peng-Fei Cui,Yu-Jing He,Jing-Cheng Zhu,Lirui Wang,Tao Pang,Yu-Kyoung Oh,Chaofeng Zhang,Hu-Lin Jiang
Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide- co -glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis. PLGA-PSPE-PEG-VA self-assembled into core-shell polymeric micelles (PVMs) at low concentrations. After loading with silibinin and siCol1α1 , the resulting chemical/genetic drug-loaded PVMs (CGPVMs) exhibited a small particle size and a slightly positive surface. CGPVMs had very low cytotoxicity and hemolytic activity in vitro and were well tolerated in mice, with no liver toxicity or inflammation. Importantly, CGPVMs effectively accumulated in fibrotic livers and specifically targeted activated HSCs. As expected CGPVMs more efficiently decreased collagen I production and ameliorated liver fibrosis compared with chemical drug (silibinin)-loaded PVMs (CPVMs) or genetic drug (siCol1α1)-loaded PVMs (GPVMs) only. These results indicate that CGPVMs are a promising tool for targeted delivery of chemogenes to activated HSCs in the treatment of liver fibrosis.
研究领域:
药学
·
材料科学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2018
·
IF 5.005
Dan Zhao,Qing Chen,Hua Song,Shuting Luo,Pingyun Ge,Yingjun Wang,Jinyuan Ma,Zhi Li,Xuemin Gao,Xuemei Zhao,Xiayiding Subinuer,Huayu Yang,Xiaojuan Jiang,Yanxin Chen,Xuan Zhu
Aim: To develop precise targeting and versatile Fe3O4@SiO2-P123/PTX-ZnPc nanoparticles (FSP-PTX-ZnPc NPs) to reverse paclitaxel (PTX)-induced multidrug resistance in breast cancer. Materials & methods: PTX and zinc (II) phthalocyanine (ZnPc) co-loaded FSP-PTX-ZnPc NPs were designed. The resulting multifunctional NPs were evaluated systematically in vitro and in vivo, and the mechanism of drug-resistance reversal was investigated. Results: The NPs enhanced drug uptake in MCF-7/PDR cells by increasing drug solubility and impairing P-glycoprotein efflux. Additionally, magnetic targeting and enhanced permeation and retention (EPR) effect enhanced drug accumulation in tumor, facilitating the chemotherapeutic and photodynamic therapy effects. Moreover, FSP-PTX-ZnPc NPs could penetrate the blood–brain barrier, a desirable trait for brain disease therapy. Conclusion: The multifunctional FSP-PTX-ZnPc NPs are an effective tool for overcoming drug resistance in breast cancer.
研究领域:
纳米技术
·
癌症研究
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2019
·Vol. 11
·期 20
·
IF 3.617
Hongmei Xu,Fangfang Teng,Feilong Zhou,Li Zhu,Yi Wen,Runliang Feng,Zhimei Song
Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.
研究领域:
药剂学
·
抗感染研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 59
·47629-47639
·
IF 3.84
Lan Bai,Fei Song,Xiao-hui Wang,Jiang-yong-quan Cao,Xue Han,Xiu-li Wang,Yu-zhong Wang
In the field of anticancer drug delivery, improving drug loading capacity of carriers and achieving efficient intracellular drug transportation simultaneously is very difficult but they are important issues for the development of chemotherapy. Herein, a reversible ligand–metal-drug coordination architecture responsive to pH was employed to construct a smart drug delivery system, in which the ligand and metal can be regarded as a harbor and an anchor to not only moor the drug (doxorubicin, DOX) but also send the cargo precisely on time. Based on the strategy, DOX loading content of the system could run up to 26.1%. Owing to the stability of coordination bonds at neutral conditions, premature drug leakage was extremely suppressed to lower than 5%, while an almost complete drug release was realized at pH 5.0 as a result of breakage of the bonds. Presence of the coordination interaction played a key role in controlled release of DOX, which followed the first-order kinetics model in the case of non-coordinated systems but the pseudo-second-order kinetics model in the case of coordinated systems. Moreover, the metal-coordinated system could effectively take DOX into HeLa cells, presenting a comparable cancer therapy effect to free DOX. This study established exploitation of coordination interaction to connect drugs and carriers as a promising way to meet urgent needs for chemotherapy.
研究领域:
药剂学
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Lipeng Qiu,Mengqin Zhu,Kai Gong,Huanhuan Peng,Lu Ge,Li Zhao,Jinghua Chen
2-(Octadecyloxy)-1,3-dioxan-5-amine (OD) with an acid degradable ortho ester group was synthesized, and conjugated to hyaluronic acid (HA) backbone to prepare pH-responsive and tumor-targeted hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) conjugates. 1 H NMR was used to confirm the structures of the OD and HOD. The studies of pH-responsive behavior showed that HOD micelles were stable under physiological conditions while they were degraded in the tumor acidic microenvironment. Doxorubicin (DOX)-loaded HOD micelles (DOX/HOD) with a narrow size distribution were prepared and characterized. The increased release of DOX from DOX/HOD micelles was presented at low pH condition. From in vitro cytotoxicity assays against MCF-7 cells, the blank micelles exhibited low cytotoxicity, but DOX/HOD micelles had the higher cytotoxicity than pH insensitive control and free DOX. Cellular uptake experiments and confocal images demonstrated that pH-sensitive DOX/HOD micelles could be internalized efficiently by CD44 receptor mediated endocytosis, and then DOX was rapidly released due to pH-induced degradable of OD to cell nucleus compared to the non-sensitive micelles. Furthermore, endocytosis inhibition studies presented that DOX/HOD micelles were internalized into cells mainly via caveolae-mediated routes. In vivo study of micelles in tumor-bearing mice indicates that HOD micelles were more effectively accumulated into the tumor tissue than HOA micelles. These results verify that the pH-sensitive HOD micellar system is a promising nanocarrier for enhanced internalization of antitumor drugs to cancer cells.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 69
·64778-64790
·
IF 3.289
Jin Ma,Ke Kang,Qiangying Yi,Zhirong Zhang,Zhongwei Gu
In this work, we reported zwitterion-functionalized “stealth” micelles for intelligent delivery of anticancer drugs. The amphiphilic polymer, poly(carboxybetaine methacrylate)-block-poly[2,2-di(acryloyloxy-1-ethoxy)propane-co-4,4-trimethylene dipiperidine [pCBMA-b-p(ADA-TMDP)], was synthesized via ATRP and subsequent Michael addition reaction. The assembled polymeric micelles were demonstrated as nanoscale (69 ± 20 nm) carriers possessing zwitterionic tentacles. Specifically, the hydrophilic zwitterionic tentacles, which were composed of the pCBMA component, could not only significantly resist protein adsorption to realize “stealth” transportation and prolong the circulation time of the drug delivery system in the blood stream, but also reverse its surface charge to facilitate cellular uptake in response to the extracellular pH environment (pH 6.8); the steady drug encapsulation cavities, as assemblies of p(ADA-TMDP) units, endowed the micelles intracellular environmental pH-responsive properties for potential endosomal escape and desired drug release after their accumulation in tumor sites through the EPR effect. The anticancer activity of these zwitterionic micelles carrying doxorubicin (DOX) was systematically studied here. At low pH (e.g., pH 5.0), cleavage of the ketal bonds of the ADA segments and protonation of the TMDP segments both contributed to the swelling and disassembly of the zwitterionic micelles. Moreover, protonation of TMDP segments caused water influx and thus facilitated micelle endosomal escape. The drug release profiles revealed that these zwitterionic micelles could accelerate drug release remarkably more (3.26-fold) at pH 5 than pH 7.4, indicating the great potential to quickly release the vast majority of the drug in tumor tissue. Both in vitro and in vivo evaluations verified the high anticancer efficiency and greatly reduced side effects of DOX-loaded zwitterionic micelles as compared with the free drug DOX·HCl.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2013
·Vol. 30
·期 12
·1034-1038
·
IF 0.857
Shaobo Ji,Wei Cao,Huaping Xu
Graphical The presence of too many reactive oxygen species (ROS) will damage cells. To eliminate ROS, a nanocomposite film containing diselenide bonds is fabricated via the layer-by-layer assembly method, using adamantane-terminated diselenide block copolymer micelles and β-cyclodextrin-modified nanoparticles as building blocks. This film possesses potential stability under the normal physiological condition and can eliminate different kinds of ROS.
研究领域:
生物医学工程
·
材料科学
·
自由基生物学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2013
·Vol. 5
·期 5
·1751-1759
·
IF 5.231
Liao Peng,Anchao Feng,Huijuan Zhang,Hong Wang,Chunmei Jian,Bowen Liu,Weiping Gao,Jinying Yuan
Voltage stimulus is considered as a clean and simple method in the field of stimuli-responsive polymer systems, in which the system based on β-cyclodextrin (β-CD) and ferrocene (Fc) has attracted considerable attention. Herein, we report voltage-responsive micelles based on the assembly of two biocompatible homopolymers, namely, the poly(ethylene glycol) homopolymer modified with β-CD (PEG–β-CD) and the poly(L-lactide) homopolymer modified with Fc (PLLA–Fc). Through host–guest interactions between β-CD and Fc, the two homopolymers connect together, forming a non-covalent supramolecular block copolymer PLLA–Fc/PEG–β-CD. PLLA–Fc/PEG–β-CD can further self-assemble to form stable micelles in aqueous solution. Through electrochemical control, a reversible assembly–disassembly transition of this micellar system was realized. Voltage-controlled drug release based on this system was also conducted successfully.
研究领域:
材料科学
·
生物医学工程
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2014
·
IF 3.916
Bin Wang,Kefu Chen,Rendang Yang,Fei Yang,Jin Liu
Ethyl cellulose macroinitiator was firstly synthesized by direct acylation of ethyl cellulose with 2-bromopropionyl bromide in a room temperature . And a light-responsive triblock copolymer of ethyl cellulose-g-poly(2-hydroxyethyl methacrylate)-g-poly(spiropyran ether methacrylate) (EC-g-PHEMA-g-PSPMA) was prepared by atom transfer radial polymerization. The amphiphilic structure of the copolymer enabled it to aggregate into spherical micelles in aqueous solution with an average diameter of 100 nm. The micelles exhibited light-responsive performance because of the SPMA monomer . The hydrophobic side chain of PSPMA became hydrophilic under UV light, which decreased the average size of the micelles. Additionally, the diameters of the micelles can be recovered when subsequently irradiated with visible light. The loading and light-triggered release profiles of model drugs were also investigated, and results showed that the release behavior can be controlled by changing the light wavelength.
研究领域:
材料科学
·
药剂学
·
高分子化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 128
·105880-105888
·
IF 3.84
Haozhe He,Yanrong Ren,Yuge Dou,Tao Ding,Xiaomin Fang,Yuanqing Xu,Hao Xu,Wenkai Zhang,Zhigang Xie
In order to improve the stability of micelles and decrease the burst release of loaded drugs, photo-cross-linked micelles were prepared via photodimerization of the coumarin moiety on amphiphilic poly(ether amine) (PEAC). The structures of the obtained monomer and polymers were confirmed by Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-vis), 1H NMR and 13C NMR (Nuclear Magnetic Resonance, NMR). PEAC could self-assemble into micelles by directly dispersing in water with a hydrophobic coumarin core and a hydrophilic poly(ethylene glycol) (PEG) shell. The photo-cross-linking process of the PEAC micelles was monitored by UV-vis spectroscopy. The morphology and size distribution of the micelles was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Anticancer drug doxorubicin (DOX) was loaded into the micelles during the process of micelle formation. Photo-cross-linked micelles showed slower drug release and cellular uptake in comparison with the uncross-linked micelles. And both DOX-loaded micelles displayed pH-sensitive release behaviours. Moreover, the DOX-loaded photo-cross-linked micelles exhibit comparative anticancer efficacy as free DOX. These results indicated that photo-cross-linked PEAC micelles can be used as potential drug carriers for intelligent drug delivery.
研究领域:
药剂学
·
材料科学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Polymer Chemistry
·
2016
·Vol. 7
·期 15
·2665-2673
·
IF 5.687
Ying Wang,Qiaojie Luo,Weipu Zhu,Xiaodong Li,Zhiquan Shen
In this work, an amphiphilic alternating multiblock copolymer poly[oligo(ethylene glycol)fumarate-co-dithiodiethanol fumarate] (POEGSSFM) with multiple enes and disulfides in hydrophobic blocks was synthesized facilely by the “one-pot” method, which can self-assemble into nano-scaled micelles and encapsulate mercapto-modified doxorubicin (DOX-SH) with 1,6-hexanedithiol into the core for in situ drug conjugation and core-crosslinking (CCL) via a thiol–ene “click” reaction, resulting in a reduction and pH dual-responsive nano-prodrug micelle (CCL-POEGSSFM-DOX). The obtained nano-prodrug micelles presented stable nano-scaled spherical particles under physiological conditions, while quickly dissociating in response to 10 mM DL-dithiothreitol (DTT). As doxorubicin (DOX) was conjugated via a pH-sensitive hydrazone linkage, the in vitro release results showed a minimized release of DOX at pH 7.4, while a rapid release at pH 5.8. Particularly, the release of DOX in an acidic environment could also be significantly accelerated by treating with DTT, owing to the cleavage of the disulfide bonds, which leads to the disassociation of the micelles. Confocal laser scanning microscopy further demonstrated that the nano-prodrug can be easily taken into cells, presenting a rapid DOX release in the cytoplasm. Cytotoxicity assay indicated that the nano-prodrug micelles exhibited excellent cytotoxic effects on HeLa cells, while blank CCL-POEGSSFM micelles were biocompatible. This facilely prepared pH and reduction dual-responsive CCL nano-prodrug would be a promising candidate for cancer chemotherapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
材料科学
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2022
·Vol. 39
·期 6
·1165-1180
·
IF 4.58
Chen Yingxian,Zhao Qian,Han Junhua,Lan Xinmiao,Che Jing,Chen Meiwan,Liang Xing-Jie,Ma Xiaowei
Purpose Methicillin-resistant Staphylococcus aureus (MRSA) infection at impaired wound is associated with high risks of developing to persistent bacterial infections since bacterial biofilm is easy to form in MRSA infected wounds. An advanced therapeutic approach to effectively penetrate and eliminate bacterial biofilm and to accelerate cell proliferation and migration at the wound is crucial. Methods The poly(ε-caprolactone)-monomethoxyl poly (ethylene glycol) (PCL-mPEG) micelles loaded with Quercetin and Rifampicin (QRMs) were prepared. Bacterial biofilm proliferation and elimination effect of QRMs were evaluated with confocal laser scanning microscopy. Antibacterial assay was further performed to detect antibacterial activity and mechanism. The cell scratch assay and cellular uptake were performed in HaCaT skin epithelial cells. Results Our results showed that the small sized QRMs could penetrate the interior of MRSA biofilm to disperse and eradicate biofilm. Then, antibiotics are released and accumulated in the acidic biofilm environment. QRMs could kill bacteria through increasing bacterial membrane permeability and altering membrane potential and membrane fluidity. Moreover, QRMs improved intracellular and cytoplasmic delivery efficiency of drugs to epithelial cells, and in the scratch test, presented a stronger ability to promote migration and proliferation of HaCaT cells compared with free drugs. Hemolysis test further proved good biocompatibility of QRMs. Conclusions QRMs could potentially be used as a novel dual-functional nanotherapeutic for anti-bacterial infection by eradicating biofilm and accelerating cells proliferation at MRSA infected wound.
研究领域:
药学
·
纳米技术
·
微生物学
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）