Journal of Nanomaterials
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2018
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IF 2.207
Dun Fan,Jingmou Yu,Ruiqiao Yan,Xiao Xu,Yunfei Wang,Xin Xie,Chaolian Liu,Yonghua Liu,Hao Huang
Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsion-solvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195–235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%–96.2%, and the loading content was 8.3%–12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC50 values of DOX/GA-GEL-2 and DOX·HCl in HepG2 cells were 0.33 and 0.66 μg/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX·HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2012
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IF 3.212
Fatima Zohra Dahmani,Hui Yang,Jianping Zhou,Jing Yao,Ting Zhang,Qiang Zhang
In order to enhance paclitaxel oral bioavailability, mixed polymeric micelles that comprised of pluronic copolymers and low molecular weight heparin-all-trans-retinoid acid (LHR) conjugate were developed. PTX-loaded mixed polymeric micelles (MPMs) were prepared by dialysis method with high drug loading 26.92 ± 2.08% and 25.82 ± 1.9% for F127/LHR and P188/LHR MPMs respectively, and were found to be spherical in shape with an average size of around 140 nm and a narrow size distribution. In vitro release study showed that pluronic/LHR MPMs exhibited delayed release characteristics compared to Taxol and faster drug release profile compared to LHR plain polymeric micelles (PPMs). The cytotoxic activity of PTX-loaded pluronic/LHR MPMs was slightly higher than LHR PPMs in MCF-7 cells ( p < 0.01). In situ effective permeability of PTX through rat small intestine was 5- to 6-fold higher with mixed micelles than that of Taxol. Moreover, pluronic/LHR MPMs achieved significantly higher AUC and C max level than both of LHR PPMs and Taxol. This enhancement might be due to the inhibition of both P-glycoprotein efflux system and cytochrome P450 metabolism by pluronic copolymers. The current results encourage further development of paclitaxel mixed polymeric micelles as an oral drug delivery system .
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PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
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2017
·Vol. 295
·期 9
·1609-1619
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IF 1.723
Ding Amin,Zhou Yifeng,Chen Pengpeng,Nie Wangyan
Amphiphilic star-shaped copolymers based on star-shaped poly(L-lactide) (s-PLLA) and poly(ethylene glycol) (PEG) (s-PLLA-PEG) were synthesized with variable molecular weights (M w ) of PEG, and the relationship between the PEG block molecular weight of s-PLLA-PEG copolymers and their micelle properties were investigated. The structure and M w of s-PLLA-PEG were characterized with 1 H NMR, GPC, DSC, and XRD. The ibuprofen (IBU)-loaded s-PLLA-PEG micelles were prepared by dialysis method. The effects of PEG block molecular weight on the morphology, particle size, zeta potential, drug loading content (LC), drug encapsulation efficiency (EE), and in vitro drug release behavior of prepared micelles were investigated. Results indicated that the average diameters, LC, and EE of IBU-loaded s-PLLA-PEG micelles increased with increasing the M w of PEG in s-PLLA-PEG copolymers. The in vitro study showed that the IBU accumulative release can be depressed by increasing the M w of the s-PLLA-PEG, and the release profiles of IBU from s-PLLA-PEG followed the Baker-Lonsdale model equation. The results suggest that structural tailoring of PEG length from s-PLLA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency.
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Oncotarget
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2016
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IF 5.008
Tingting Meng,Jingwen Liu,Lijuan Wen,Ming Yuan,Bolin Cheng,Yingwen Hu,Yun Zhu,Xuan Liu,Hong Yuan,Fuqiang Hu
Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro , on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo , the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What's more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.
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PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2016
·Vol. 68
·期 6
·751-761
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IF 2.363
Rongbin Huang,Lei Xiang,Ying Liu,Xiangping Deng,Xuan Cao,Lanfang Li,Cuiyun Yu,Yanming Chen,Guotao Tang
ObjectivesTo develop an acid trigger release of antitumour drug delivery carriers, pH-sensitive amphiphilic poly (ethyleneglycol)-imine-benzoic-dipalmitate (PEG-I-dC16) polymers were designed and synthesized and the drug-loaded micelles were evaluated in vitro.MethodsPEG-I-dC16 synthesized by Schiff base synthetic method and characterized by 1H-NMR. To determine the drug-loading capacity, doxorubicin (DOX) was encapsulated in the micelles using membrane dialysis method. Zeta potential, particle size, drug-loading capacity, in vitro drug release in different pH conditions and cytotoxicity evaluation of micelles were carried out comparing with non-acid liable PEG–amide–benzoic–dipalmitate (PEG-A-dC16) polymers micelles. The cellular uptake and intracellular distribution of DOX were detected by flow cytometry and confocal laser scanning microscope.Key findingsDrug-loading capacity and encapsulation efficiency of micelle (PEG molecular weight 2k) were 12.7 ± 1.1% and 49.8 ± 2.2%, respectively. The average particle size was 72.3 ± 2.5 nm. The DOX release rate of PEG-I-dC16 micelles is much higher at pH 6.5 than at pH 7.4. DOX cellular uptake and nuclear accumulation of PEG-I-dC16 micelles were more efficiency than that of PEG-A-dC16 micelles.ConclusionThe pH-sensitive PEG-I-dC16 micelles could be a promising drug delivery system for anticancer drugs.
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高影响因子
DRUG DELIVERY
·
2016
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IF 4.843
Chang Li,Yan Shen,Chunmeng Sun,Nihad Cheraga,Jiasheng Tu
To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.
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RSC Advances
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2016
·Vol. 6
·期 33
·27542-27556
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IF 3.289
Chenfeng Xu,Yu Ding,Jiang Ni,Lifang Yin,Jianping Zhou,Jing Yao
Docetaxel (DTX) has profound effects on several hepatic cancer (HC) cells, but shows unsatisfactory clinical efficacy due to the lack of tumor specificity and p-gp mediated drug efflux. Herein, a novel targeted drug delivery nanosystem based on hyaluronic acid (HA) and quercetin (QU) was designed to improve the in vivo therapeutic efficacy of DTX on HC through HA-CD44 mediated targeting and QU-based p-gp efflux inhibition. DTX-loaded HA–QU polymeric micelles (DTX/HA–QU PMs) displayed a mean particle size of 176.8 ± 3.4 nm with a low polydispersity index (<0.2). The drug loading and entrapment efficiency were 23.6 ± 1.3% and 86.8 ± 1.8%, respectively. Not only did the nanosystem facilitate cellular uptake via HA-CD44 mediated endocytosis, but it also preferentially accumulated at the tumor site via the EPR effect. Moreover, DTX/HA–QU PMs showed prolonged circulation time and high stability in the bloodstream, and achieved AUC0–∞ and t1/2 values that were 3.0-fold and 5.51-fold higher than those of Taxotere®, respectively. In addition, an in vitro cytotoxicity study showed that DTX/HA–QU PMs were 13.6-fold more effective than Taxotere®, judging by the IC50. Importantly, DTX/HA–QU PMs presented the highest antitumor efficacy in a xenograft tumor-bearing mice model and the tumor inhibition ratio was 73.91%. Meanwhile, DTX/HA–QU PMs could down-regulate p-gp expression in tumor cells. These results suggested that the targeting moiety and p-gp efflux inhibitory property help DTX to accumulate at the tumor site and improve its antitumor efficacy in vivo.
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RSC Advances
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2016
·Vol. 6
·期 17
·13698-13709
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IF 3.289
Ying Hao,YiXing Huang,YunQi He,JinRong Peng,LiJuan Chen,Xun Hu,ZhiYong Qian
In this study, we successfully prepared MPEG–PDLLA polymer micelles with two different particle sizes, A and B. DLS and TEM assays demonstrated that the particle sizes of the polymer micelles A and polymer micelles B were about 25 nm and 150 nm respectively. The stability of the MPEG–PDLLA polymer micelles in vitro revealed that the free Cy5.5 dye had been successfully loaded into the polymer micelles as a fluorescence marker and the fluorescence wasn’t quenched until 72 h. The cellular uptake of the polymer micelles was time-dependent and micelles A (particle size 25 nm) showed a higher efficiency to be internalized into the cytoplasm of MCF-7 cells than micelles B (particle size 150 nm). Furthermore, in vivo and in vitro biodistribution and tumor-targeting of polymer micelles MPEG–PDLLA were investigated in female MCF-7 tumor-bearing balb/cA-nu mice with an IVIS imaging system. The results showed that polymer micelles A (particle size 25 nm) had a time dependent biodistribution and tumor site accumulation in mice bearing MCF-7 tumors. Meanwhile, the NIR fluorescence intensity of polymer micelles B (particle size 150 nm) in tumor sites showed a pattern of a rise, a peak and then a decline. What’s more, the distribution of the polymer micelles in the tissue slices demonstrated the same results. Consequently, the results indicated that the micelles with a smaller particle size (25 nm) could be more efficiently internalized into cells and increase the enhanced permeation and retention (EPR) effect in tumor tissue. Therefore, a reasonable small size of micelles may be a key factor for a high-performance anti-cancer drug delivery system.
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International Journal of Nanomedicine
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2017
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IF 4.3
Lei Yang,Zhenghai Zhang,Jian Hou,Xin Jin,Zhongcheng Ke,Dan Liu,Mei Du,Xiaobing Jia,Huixia Lv
Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d -alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC 50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 μg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group ( P <0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK.
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Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Hongxia Liu,Shuqin Wu,Jingmou Yu,Dun Fan,Jin Ren,Lei Zhang,Jianguo Zhao
Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed. CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is 0.047 mg/mL, and its mean diameter is 387 nm. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the micelles with high loading efficiency. Reduction-sensitive micelles and reduction-insensitive control micelles displayed similar DOX release behavior in phosphate buffered saline (PBS, pH 7.4). Notably, DOX release from the reduction-sensitive micelles in vitro was accelerated in the presence of 20 mM glutathione-containing PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles exhibited intracellular reduction-responsive characteristics in human gastric cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM). Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than reduction-insensitive control micelles in HGC-27 cells. These results suggested that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular targeted carriers of anticancer drugs.
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高影响因子
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
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2016
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IF 4.179
Yuan Wang,Yan-Ling Luo,Feng Xu,Ya-Shao Chen,Wei Tang
Ferrocene-containing amphiphilic block copolymers , poly(2-acryloyloxyethyl ferrocenecarboxylate)- block -poly(2-(dimethylamino) ethyl methacrylate) (PAEFc- b -PDMAEMA), were synthesized via sequential ATRP , and self-assembled into globular nanoscaled micelle aggregates. The copolymer micelles exhibited reversible redox on-off switch feature, which was mediated by using H 2 O 2 , KMnO 4 , NaClO and FeCl 3 as a model of oxidants and ascorbic acid as a model of reductants. The micelle nanoparticles were used to load and deliver anticancer drug, 10-hydroxycamptothecine, finding that the encapsulated drug was rapidly delivered by selectively responding to redox environments in cancer cells. MTT assays were performed to uncover cytotoxicity of the developed copolymer micelles and potentiality used for cancer therapy.
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APPLIED SURFACE SCIENCE
·
2014
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IF 2.538
Chunhua Gu,Huan Zhang,Meidong Lang
Amphiphilic chitosan- graft -poly(ɛ-caprolactone) (CS- g -PCLs) copolymers were synthesized by a homogeneous coupling method and characterized by 1 H NMR, FTIR and ninhydrin assay. The graft copolymers were subsequently self-assembled into micelles, which were measured by DLS and TEM. The particle size of the micelles decreased as the segment grafting fraction was increased. Thereafter, silver nanoparticles were prepared in the presence of chitosan-based micelles under UV irradiation. The molar ratio and radiation time of silver to micelles were optimized with process monitored via UV–vis spectrophotometer. DLS and TEM were used to illustrate the particle structure and size while XRD patterns were applied to characterize the crystal structures of polymer-assisted silver nanoparticles. Films impregnated with silver nanoparticles were conducted with results of strong antimicrobial activities against Escherichia coli and Staphylococcus aureus as model Gram-negative and positive bacteria.
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危险品化学品经营许可证（带存储）