RSC Advances
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2019
·Vol. 9
·期 68
·40131-40145
·
IF 3.049
Jizheng Song,Yuling Liu,Longfei Lin,Ye Zhao,Xiuqing Wang,Ming Zhong,Tanggui Xie,Yuting Luo,Shaojing Li,Ruocong Yang,Hui Li
Curcumin (CUR), a natural polyphenolic compound existing in plants, exhibits anticancer potential in inhibiting the growth of various types of human cancer. However, the poor aqueous solubility and low bioavailability limit its clinical applications. pH-sensitive macromolecule F68-acetal-PCL (FAP) and active targeting macromolecule F68-glycyrrhetinic acid (FGA) were designed to fabricate mixed micelles for efficient delivery of CUR. The thin film hydration method was used to prepare CUR loaded mixed (MIX/CUR) micelles. The drug loading rate (DL) of MIX/CUR micelles was 6.31 ± 0.92%, which remained stable for 15 days at 4 °C. The particle size and zeta potential of the MIX/CUR micelles were 91.06 ± 1.37 nm and −9.79 ± 0.47 mV, respectively. The MIX/CUR micelles exhibited pH sensitivity in a weak acid environment, and showed rapid particle size variation and drug release. In addition, in vitro tests demonstrated that MIX/CUR micelles induced higher cytotoxicity and apoptosis than free CUR, non-pH-sensitive F68-PCL (FBP)/CUR micelles and pH-sensitive FAP/CUR micelles in SMMC7721 and Hepa1-6 cells. Besides, mixed micelles were more effective than FBP and FAP micelles in a cell uptake experiment, which was medicated by a GA receptor. All in all, these results indicated that MIX/CUR micelles could be regarded as an ideal drug administration strategy against hepatoma carcinoma cells.
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JOURNAL OF POLYMER RESEARCH
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2019
·Vol. 26
·期 5
·1-12
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IF 1.53
Chen Dan,Gong Feirong,Han Xiaoxiong,Chi Lili,Sun Jing,Shen Yaling
Conventional self-assembled polymeric micelles typically lose their loaded drugs after systemic administration. To resolve this issue, the aim of the present study was to develop a novel polymer, methoxy-poly (ethylene glycol)-block-poly ( d , l -lactic acid) grafted with four lipoic acids (mPEG-PLA-(LA) 4 ), to prepare curcumin-loaded core cross-linked polymeric micelles (CCM). Nitrogen and alkalescent buffer (pH 8.5) were beneficial for cross-linking, and the cross-linking was nearly complete within 30 min. The micelle preparation parameters were optimized through both a single-factor experiment and orthogonality test. The choice of cryoprotector had the most important effect on micelle solution reconstruction and almost challenged our perceptions about cryoprotector. In addition the drug loading capacity greatly affected the stability of micelles. Moreover, a method for determining the cross-linking density was established, and the result of gel permeation chromatography indirectly demonstrated that dozens of polymers had successfully formed CCM. The CCM significantly enhanced stability under non-reductive conditions and could be reversibly broken in a reductive environment. Curcumin-loaded CCM also showed glutathione-response cytotoxicity to cancer cells. Overall, this fundamental study suggests CCM as a potential carrier for achieving improved controlled drug delivery.
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BIOMACROMOLECULES
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2019
·
IF 5.667
Yanqian Wu,Yi Xiao,Yushu Huang,Yanyun Xu,Donglei You,Wei Lu,Jiahui Yu
A biodegradable brush-type copolymer PHF-g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.
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Theranostics
·
2019
·
IF 8.063
Yanan Tan,Yun Zhu,Lijuan Wen,Xiqin Yang,Xuan Liu,Tingting Meng,Suhuan Dai,Yuan Ping,Hong Yuan,Fuqiang Hu
Responsive drug release in tumor mitochondria is a pre-requisite for mitochondria-targeted drug delivery systems to improve the efficacy of this promising therapeutic modality. To this end, a photothermal stimulation strategy for mitochondria-responsive drug release along with heat shock is developed to maximize the antitumor effects with minimal side effects. Methods: This strategy relies on mitochondrial-targeted delivery of doxorubicin (DOX) through a photothermal and lipophilic agent IR-780 iodide (IR780)-modified glycolipid conjugates (CSOSA), which can synergistically triggers high-level reactive oxygen species (ROS) to kill tumor cells. Results: Specifically, upon laser irradiation, the photothermal conversion by IR780-CSOSA can not only weaken the hydrophobic interaction between the core of micelles and DOX and trigger unexpected micelle swelling to release DOX in mitochondria for the amplification of ROS, but also induce mitochondria-specific heat shock to promote the fast evolution of ROS at the same locus to eradicate cancer cells in a more effective way. Furthermore, IR780-CSOSA micelles may independently realize the real-time diagnosis and imaging on multiple tumor models. Deep penetration into tumors by IR780-CSOSA/DOX micelles can be manipulated under laser irradiation. Conclusion: Such multifunctional IR780-CSOSA/DOX micelles with integration of mitochondria-responsive drug release and heat shock are demonstrated to be superior to the non-mitochondria-responsive therapy. This study opens up new avenues for the future cancer diagnosis and treatment.
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ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Zhaoyan Yang,Jingkun Xu,Shenfei Zong,Shuhong Xu,Dan Zhu,Yizhi Zhang,Chen Chen,Chunlei Wang,Zhuyuan Wang,Yiping Cui
Lead halide perovskite nanocrystals (NCs) are promising optical materials in many fields. However, their poor moisture stability, significant toxicity, and difficulty to be further functionalized greatly hinder their applications in bioimaging. Here, a universal strategy is demonstrated by simply encapsulating CsPbX3 (X = Cl, Br, I) NCs into phospholipids to achieve CsPbX3–phospholipid micelles (CsPbX3@phospholipid) as probes for multiplex encoding cellular imaging or tumor-targeted imaging. The layer of phospholipids endows CsPbX3 NCs with superior water-resistant characteristics, the ability to be further biofunctionalized, and greatly improved biocompatibility. The CsPbX3@phospholipid micelles exhibited strong luminescence with narrow fwhm in water for more than four months. Specifically, even after being modified with folic acid, the bright fluorescence of the micelles was well retained, which were employed for the targeting of Hela cells. Finally, the greatly reduced toxicity of the CsPbX3@phospholipid micelles was verified using HeLa cells and zebrafish as in vitro and in vivo models, respectively.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Lifen Wang,Pengpeng Xue,Mengqi Tong,Rui Chen,Waigeng Yang,Deli ZhuGe,Jiandong Yuan,Qing Yao,Yingzheng Zhao,Helin Xu
Inflammatory bowel diseases (IBDs) are chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Laquinimod (LAQ), a poorly water-soluble compound, was proved to be effective for colitis remission at low dose of 0.5 mg/kg in patients with Crohn’s disease. Due to its extremely low solubility in water, it was difficult to develop an injectable liquid dosage form. Herein, D-α-Tocopheryl polyethylene glycol-1000 succinate (TPGS) polymeric micelles were developed as a delivery vehicle of LAQ for the management of inflammatory bowel disease. Using the LAQ/TPGS ratio of 1:100, LAQ-loaded micelles were successfully prepared by thin-film dispersion method. The solubility of LAQ in water was significantly increased from 10.5 μg/mL in pure water to 500 μg/mL in TPGS micelles. LAQ-loaded micelles of TPGS exhibited the fine particle size of 34.6 nm and Zeta potential of -0.67 mV. Moreover, the good stability of LAQ-loaded micelles in physiology-mimicking medium was confirmed by detecting their particle size, zeta potential and leakage of the loading drug. Therapeutic effect of LAQ-loaded micelles on DSS-induced mice was proved by detecting DAI score, colon length and loss of body weight. Moreover, the morphology and colonic mucosal barrier of the injured colon of DSS-induced mice was largely recovered after treatment with LAQ-loaded micelles. Meanwhile, the inflammation of colitis colon was also obviously alleviated by LAQ-loaded micelles. Conclusively, polymeric micelles of TPGS may be a promising delivery vehicle of LAQ for the management of inflammatory bowel disease.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
·
IF 1.911
Caochuan Feng,Xiaoxiong Han,Lili Chi,Jing Sun,Feirong Gong,Yaling Shen
Combination therapy of two or more drugs has gradually become of outmost importance in cancer treatment. Cabazitaxel (CTX) is a taxoid drug and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of TNF superfamily. In this study, we prepared TRAIL-modified and CTX-loaded polymer micelle (TRAIL-M-CTX). This nanoparticle was self-assembled from biodegradable amphiphilic copolymers, monomethoxyl poly(ethylene glycol)–b-poly(DL-lactide) (mPEG-PLA) and COOH-PEG-PLA, via a nanoprecipitation method and were modified with the TRAIL protein, resulting in a particle size of 39.75 ± 0.17 nm in diameter and a drug encapsulation efficiency of 95.52 ± 1.69%. The successful coupling was confirmed by 1H NMR, FTIR spectroscopy, and DLS article size measurement. Pharmacodynamic analysis in two human cancer cell lines with different TRAIL sensitivities showed that TRAIL-M-CTX has a significantly better anticancer efficacy than the individual CTX and TRAIL protein. Importantly, TRAIL-M-CTX showed synergistic effects against TRAIL-insensitive cells (MCF-7). A study of cellular uptake implied that the modified micelles were internalized into MCF-7 cells more effectively than unmodified micelles, owing to the coupled TRAIL protein. A cell cycle assay of MCF-7 cells revealed that TRAIL-M-CTX significantly increased the sub-G1 population compared with CTX or TRIAL, thus, facilitating cancer cell apoptosis. These results suggest that TRAIL-M-CTX micelles have potential as a cancer chemotherapy formulation.
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CARBOHYDRATE POLYMERS
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2018
·
IF 5.158
Xiaoying Wang,Yangli Guo,Liangzhen Qiu,Xiaying Wang,Tonglei Li,Lifeng Han,Huizhi Ouyang,Wei Xu,Kedan Chu
An amphiphilic carboxymethyl chitosan-rhein (CR) conjugate was prepared, characterized, and evaluated as a potential carrier material for oral delivery of paclitaxel (PTX). CR conjugate self-assembled in aqueous environment into CR polymeric micelles (CR PMs). The drug loading capacity and entrapment efficiency of PTX-loaded CR PMs were 35.24 ± 1.58% and 86.99 ± 12.26%, respectively. Pharmacokinetic results indicate that PTX-loaded CR PMs could significantly enhance the oral bioavailability of PTX. Confocal imaging of intestinal sections verified many of CR PMs were absorbed as whole through the intestinal membrane. The cytotoxicity assays in Caco-2 cells and in vivo antitumor efficacy showed that PTX-loaded CR PMs had a stronger antitumor efficacy. A synergistic antitumor effect between CR conjugate and PTX was proven in MCF-7 cells and antitumor efficacy studies. The investigation of CR conjugate developed in this study showed that CR PMs are promising for oral delivery of water-insoluble antitumor drugs.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
·
IF 3.909
Cihui Tian,Sajid Asghar,Yurui Xu,Zhipeng Chen,Jingwei Zhang,Qineng Ping,Yanyu Xiao
Redox-sensitive micelles based onhydrophilic hyaluronic acid-ss-hydrophobic curcumin conjugate were designed as a novel delivery system for gliomas targeting. Furthermore, the obtained micelles were further functionalized with Tween 80 (CUR-THSC) for better brain penetration. Dynamic light scattering experiment and in vitro release study showed that the synthetic disulfide-linked conjugate possessed redox-sensitivity under high glutathione conditions. Spherical micelles with a mean particle size of 74.2 nm, negative zeta potential (−30.25 mV), high entrapment efficiency (94.12%) and drug loading (8.9%) were obtained. XRD analysis of micelles revealed amorphous form of the encapsulated drug. CUR-THSC micelles showed good plasma stability and did not induce any hemolysis in erythrocytes. In addition, highest cytotoxicity in G422 cells was observed compared to the free curcumin group and non-sensitive micelles group. These results indicate that the Tween 80-modified hyaluronic acid-ss-curcumin micelles could emerge as a promising platform for the delivery of curcumin in the treatment of gliomas.
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Liqiu Chu,Yutong Zhang,Zhipan Feng,Jueying Yang,Qingquan Tian,Xianping Yao,Xinqi Zhao,Huimin Tan,Yu Chen
Magnetic nanoparticle-embedded polymeric micelles (MNP-PMs) prepared with amphipathic polymers are an important sustained-release carrier for hydrophobic drugs. The amphipathic chitosan derivatives (ACDs) based stimuli-responsive slow-release carriers have attracted considerable attentions because of the bioactivities and modifiability of chitosan. In the current study, a series of ACDs including alkylated N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (alkyl-HTCC) and alkylated polyethylene glycol N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (alkyl-PEG-HTCC) were prepared by the reductive amination of HTCC and PEG-HTCC, and their structures and properties were characterized. Octyl-HTCC/O-Fe 3 O 4 and octyl-PEG-HTCC/O-Fe 3 O 4 MNP-PMs were prepared by the hydrophobic interactions between the corresponding ACDs and oil soluble Fe 3 O 4 magnetic nanoparticles (O-Fe 3 O 4 MNPs), and characterized for the structure, magnetic performance and surface charge state. Their potential application as a drug delivery carrier was investigated upon the embedding efficiency and pH dependent sustained-release performance using the hydrophobic drug, paclitaxel (PTX), as a model drug. Our work has provided a new application strategy of ACDs in the multi-functional drug delivery carrier.
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AICHE JOURNAL
·
2014
·Vol. 61
·期 1
·35-45
·
IF 2.581
Feng Xu,Jing-Wen Xu,Bi-Xia Zhang,Luo Yan-Ling
Novel tri-armed star polystyrene-block-poly(N-isopropylacrylamide) block copolymers with trimesic acid as central molecules were synthesized by successive two-step atom transfer radical polymerization, and confirmed by Fourier-transform infrared spectra, 1 H nuclear magnetic resonance, and laser light scattering gel chromatography system. The copolymers could self-assemble into spherical core-shell micelles in aqueous media independent on drug loading. Physicochemical properties of the blank and drug-loaded micelles were examined by surface tension, fluorescence spectroscopy, UV-vis, transmission electron microscope, and dynamic light scattering measurements. The copolymer micelles exhibited thermo-triggered phase transition, with low critical solution temperature of 33.7 and 34.6°C, varying with copolymer compositions. The critical aggregate concentrations were 11.62 and 47.61 mg L −1 , and hydrodynamic diameters from 200 to 220 nm. Water-insoluble 10-hydroxycamptothecine was encapsulated into the micelle aggregates to investigate the change in the resulting physicochemical parameters, thermo-triggered in vitro drug release, and the applicability as drug targeting release carriers. MTT assays were carried out to uncover cytotoxicity of the newly developed micelle-based drug formulations. © 2014 American Institute of Chemical Engineers AIChE J , 61: 35–45, 2015
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APPLIED SURFACE SCIENCE
·
2014
·
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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