COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2013
·
IF 2.108
Yan-Ling Luo,Rui-Juan Huang,Li-Li Zhang,Feng Xu,Ya-Shao Chen
A thermo- and pH-stimuli-responsive brush-shaped graft copolymer based on macromonomers acrylate terminated PMAA–CH=CH 2 and PNIPAAm–CH=CH 2 was synthesized, which is composed of poly(methacrylic acid) (PMAA) and poly( N -ispropylacrylamide) (PNIPAAm) as graft brushes, named PMAA- b -PNIPAAm. The copolymers can self-assemble to form spherically-shaped core-shell nanostrucrued micelles in different media, with the critical micelle concentration (CMC) in aqueous solution from 9.24 to 32.81 mg L −1 , and the hydrodynamic diameters varying with pH and temperature, from 120 to 195 nm. The resultant nanoscale copolymer micelles exhibited pH-triggered thermoresponsive behavior, with low critical solution temperature (LCST) about 38.2–47.5 °C. The polymer micelle nanoparticles were observed to be stable under simulated physiological conditions. The cytotoxicity studies by MTT assay and in vitro prednisone drug release demonstrated that the PMAA- b -PNIPAAm copolymer micelles were not directly toxic to L929 mouse embryonic fibroblasts and the in vitro release behavior under various physiological environments depended upon pH and temperature change. Therefore the as-prepared brush-shaped graft copolymer micelle nanoparticles may serve as a promising “intelligent” drug delivery carrier.
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Yong Sun,Yihang Huang,Shaoquan Bian,Jie Liang,Yujiang Fan,Xingdong Zhang
Reduction-breakable core–shell type polymeric micelles from reduction-degradable amphiphilic polyethylene glycol- b –polyamide amine- b –polyethylene glycol triblock copolymers (PEG- b –PAA- b –PEG) were prepared as new drug carriers of methotrexate (MTX) for cancer chemotherapy. The PEG- b –PAA- b –PEG copolymers were synthesized in a simple one-step process under mild condition through Michael addition. Spherical micelles with diameters ranging from 65 to 123 nm were successfully fabricated from the copolymers. These micelles could effectively encapsulate the anti-cancer drug MTX in the core with drug loading content around 13%. The incorporation of MTX resulted in a little size increase but did not influence the morphology of micelles. The drug was hardly released from the micelles in normal condition without DDT as the reductant, but fast released up to 100% within 24 h when the structure of micelle core was broken in the presence of DTT, thus provided a potential tool for tumor targeting delivery of MTX using the higher concentration of reductant in tumor tissues. The proliferation inhibition experiments demonstrate that MTX-encapsulated micelles show significant cytotoxicity to KB, HepG2 and 4T1 tumor cells, especiallythe 4T1 cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 7
·e0180037
·
IF 2.806
Weiping Ji,Bo Wang,Qiuping Fan,Chao Xu,Youwu He,Youfen Chen
Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran- g -indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2017
·Vol. 218
·期 19
·1700148
·
IF 2.5
Pingping Wang,Shubo Cao,Yongbin Zhao,Tomokazu Iyoda,Aihua Chen
Detailed investigations on the self-assembly of amphiphilic star block copolymers composed of three-arm poly(ethylene oxide) (PEO) and poly(methacrylate) (PMAAz) with an azobenzene side chain (denoted as 3PEO- b -PMAAz) into stable spherical aggregates with clear lamellar stripes in solution are demonstrated. Four block copolymers, 3PEO 12 - b -PMA(Az) 33 , 3PEO 22 - b -PMA(Az) 31 , 3PEO 22 - b -PMA(Az) 62 , and linear PEO 68 - b -PMA(Az) 31 , are synthesized. The liquid crystalline properties of the block copolymers are studied by differential scanning calorimetry, polarized optical microscopy techniques, and wide-angle X-ray diffraction. The morphologies of the compound micelles self-assembled in tetrahydrofuran (THF)/water mixtures are observed by means of transmission electron microscopy and scanning electron microscopy. The size of the spherical micelles is influenced by the self-assembly conditions and the lengths of two blocks. The well-defined three-arm architecture of the hydrophilic blocks is a key structural element to the formation of stable spherical compound micelles. The micelle surface integrity is affected by the lengths of PEO blocks. The lamellar stripes are clearly observed on these micelles. This work provides a promising strategy to prepare functional stable spherical compound micelles self-assembled by amphiphilic block copolymers in solution.
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 34
·21328-21335
·
IF 3.108
Rujiang Ma,Chuan Zhang,Yong Liu,Chang Li,Yanling Xu,Baoxin Li,Yunliang Zhang,Yingli An,Linqi Shi
Amphiphilic block copolymer micelles in aqueous solution have been used extensively in delivery of hydrophobic drugs with the hydrophobic core serving as the reservoir. However, encapsulation of hydrophilic drugs by polymeric micelles with hydrophobic core is relatively difficult because of the poor interaction between them. Herein, we report a novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug loaded, via direct subcomponent self-assembly of block copolymer poly(ethyleneglycol)-block-poly(L-lysine) (PEG-b-PLys), 2-formylbenzeneboronic acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (e.g. capecitabine (CAPE)) under physiological pH 7.4 based on the synergistic formation of an iminoboronate structure. The PEG-b-PLys/2-FPBA micelles without CAPE are well-characterized in terms of micellization mechanism, size, morphology, pH- and GSH-responsiveness. Encapsulation of CAPE by forming PEG-b-PLys/2-FPBA/CAPE complex micelles via synergistic formation of the iminoboronate structure is discussed and pH- and GSH-responsive drug-release studies are carried out. The complex micelles are stable under physiological neutral conditions but could be destroyed in response to the stimuli of physiological acidic condition (pH 5.0) and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are successfully achieved. The drug-loaded complex micelles could be endocytosed by HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of complex micelles could be used as a promising platform for the delivery of hydrophilic 1,2-diol-containing drugs.
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Gan Liu,Hongjun Gao,Yixiong Zuo,Xiaowei Zeng,Wei Tao,Hsiang-i Tsai,Lin Mei
Combining sufficient stability during circulation and desirable drug release is still a great challenge for the clinical applications of nanocarriers. To satisfy this demand, we developed a novel unimolecular micelle (UM) to deliver the antitumor agent 1,2-diaminocyclohexane-platinum(II) (DACHPt) for enhanced therapy of lung cancer. This DACHPt-loaded UM (UM/DACHPt) was formed through chelate complexation between DACHPt and a hydrophilic and biodegradable dendritic block copolymer poly(amidoamine)-polyglutamic acid-b-polyethylene glycol (PAM-PGlu-b-PEG), which was composed of generation 3 PAMAM (PAMAM-G3), polyglutamic acid, and long-circulating polymer PEG. This UM/DACHPt displayed robust stability and would effectively inhibit the undesired release under physiological condition, thus exhibiting much longer in vivo half-life than diblock copolymer micelles. With significant in vitro cell cytotoxicity to A549 lung cancer cells, this UM/DACHPt demonstrated efficient antitumor efficacy on an A549 xenograft tumor model with negligible tissue cytotocxity. Therefore, this UM/DACHPt provides a promising new strategy for lung cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Qin Wang,Jiayu Jiang,Wenfei Chen,Hao Jiang,Zhirong Zhang,Xun Sun
Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis , but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block–poly (εcaprolactone) (PCL–PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8 mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL–PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL–PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2017
·Vol. 38
·期 12
·1655-1662
·
IF 3.223
Dong Xin-yue,Lang Tian-qun,Yin Qi,Zhang Peng-cheng,Li Ya-ping
Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2017
·
IF 1.9
Peizong Deng,Fangfang Teng,Feilong Zhou,Zhimei Song,Ning Meng,Runliang Feng
Ketoconazole is a broad spectrum imidazole antifungal drug. For the treatment of superficial fungal infections with ketoconazole, it needs to be permeated to deep skin layers. In order to develop topical formulation of ketoconazole for improving its skin deposition and water-solubility, ketoconazole-loaded methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) micelles were developed through thin-film hydration method. Particle size, drug loading capacity, infrared spectrum and X-ray diffraction of drug-loaded micelles were characterized. The optimal drug formulation was selected for skin delivery and deposition investigation performed by use of mice skin, and its in vitro release and antifungal activity were also investigated. Penetration and distribution in the skin were also visualized using fluorescein-loaded micelles and fluorescence microscopy. The drug-loaded micelles were obtained with encapsulation efficiency of 86.39% and particle diameter of about 12 nm. The micelles made ketoconazole aqueous solubility increase to 86-fold higher than crude one. Ketoconazole-loaded micelles showed no skin permeation of ketoconazole, obviously enhance skin deposition and demonstrated similar antifungal activity as compared with marketed ketoconazole cream. Fluorescein-loaded micelles displayed higher skin deposition than fluorescein water solution. These results demonstrate that the MPEG-PVL micelle is a potential delivery system for ketoconazole in the field of skin delivery.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 8
·1480-1488
·
IF 4.872
Yu-Bo Long,Wen-Xing Gu,Chengcai Pang,Jianbiao Ma,Hui Gao
It is still a major challenge for targeted cancer chemotherapy to design a stable biocompatible micellar drug delivery system. To address this dilemma, novel responsive cross-linked micelles (x-micelles) based on polyurethane with photo-responsive coumarin derivatives and pH-responsive hydrazone groups were synthesized. The polymers could be self-assembled into micelles using a typical and facile way. The x-micelles were stable at physiological conditions after UV light induced cross-linking, and can be disassociated under acidic condition. The drug loading content (DLC) and the encapsulation efficiency (EE) of the obtained x-micelles (15.2% and 60.8% respectively) were higher than those of micelles (9.8% and 39.2% respectively), and the DOX release rate of x-micelles was also improved. For targeted therapy, folic acid (FA) was then conjugated to x-micelles, resulting in x-micelles–FA. Cellular viability experiments show that both x-micelles and micelles had a low cytotoxicity and good biocompatibility of up to 1000 μg mL−1, and DOX-loaded x-micelles–FA and x-micelles exhibited half-maximal inhibitory concentration (IC50) values of 1.17 and 2.40 μg mL−1, respectively, to HeLa cells, but have lower cytotoxicity to L929 cells. The pH-responsive x-micelles–FA exhibited superior extracellular stability but activated intracellular drug release. We have demonstrated that the polyurethane with UV- and pH-responsive properties as a novel platform for tumor-targeting drug delivery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Soft Matter
·
2016
·Vol. 13
·期 3
·670-676
·
IF 3.798
Juan Zhang,Yingxia Wang,Guiying Xu,Meinqin Lin,Tianyu Fan,Zihao Yang,Zhaoxia Dong
From catanionic fluoro-/hydro-carbon mixtures of fluoroacetic acid (CF3COOH) and tetradecyldimethylaminoxide (C14DMAO) in water, viscoelastic wormlike micelles are successfully constructed which are determined by cryo-TEM measurements. It is found that the formation and rheological behavior of the wormlike micelles are greatly affected by the total concentration and mixing ratio of CF3COOH and C14DMAO as well as temperature. The driving force for the formation of wormlike micelles here is considered to be the electrostatic attractive interaction between the two molecules which is confirmed by 1H NMR measurements. As far as we know, such wormlike micelles formed from the catanionic mixtures of fluorofatty acids and hydrocarbon surfactants have been rarely reported. Our work provides a simple method through mixing a perfluorofatty acid with a hydrocarbon surfactant to construct and understand the formation mechanism of catanionic fluoro-/hydro-carbon wormlike micelles, which should be a great advance in the fundamental research of wormlike micelles.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2016
·Vol. 7
·期 26
·4352-4366
·
IF 5.687
Changyu He,Zhen Zhang,Qinglai Yang,Qing Chang,Zhifeng Shao,Bing Gong,Yu-Mei Shen,Bingya Liu,Zhenggang Zhu
A reductive tri-block copolymer PEG-SS-PLA-SS-PEI with a double disulphide linkage in the backbone directed by H-bonding association was synthesized and self-assembled into cationic polymeric nanomicellar particles for in vivo antimiRNA delivery with an average diameter of 68 nm and a zeta potential of approximately 39 mV. The chemical structure of the copolymer was well characterized by 1H NMR and GPC. The cationic polymeric nanomicellar particles could be unpacked in an intracellular reductive environment (GSH) leading to the release of encapsulated antimiRNA. MTT assays in vitro showed no significant cytotoxicity of SGC7901 gastric cancer cells incubated with PEG-SS-PLA-SS-PEI micelles. The in vitro study indicated that the micelle-based antimiR-21 delivery system could effectively facilitate cellular uptake and greatly down-regulate the expression level of miR-21 in SGC7901 cell lines, which was comparable to Lipofectamine™ 2000. The down regulation of miR-21 remarkably induced apoptosis, suppressed the tumor cell migration and invasion, and increased the expression of target genes such as phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Programmed Cell Death Protein 4 (PDCD4). More importantly, the in vivo systemic administration of the micelles/antimiR-21 complex in a gastric cancer model significantly inhibited tumor growth and increased the expression of target genes. The nanoparticle based on the PEG-SS-PLA-SS-PEI copolymer would be a safe and efficient carrier for delivery of therapeutic antimiRNA, which shows a prospective therapy method in gastric cancer.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）