NANOTECHNOLOGY
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2013
·Vol. 24
·期 14
·145101
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IF 3.842
Dao-Lu Tang,Fei Song,Cheng Chen,Xiu-Li Wang,Yu-Zhong Wang
Increasing attention has recently been paid to the fabrication of drug delivery systems with excellent cell internalization and intracellular drug release properties. In this study, an amphiphilic block copolymer of chitosan was synthesized for the first time, which can self-assemble into micelles in a neutral aqueous solution but partially disassemble in an acidic endosomal/lysosomal environment. The antitumor drug, camptothecin (CPT), was encapsulated in the cores of the micelles for tumor cell therapy. In vitro drug release studies demonstrated that the micelles presented a much faster release of CPT at pH 5.0 than at pH 7.4. Blank micelles were found to be nontoxic in preliminary in vitro cytotoxicity assays. Cell experiments showed that the CPT-loaded micelles could be effectively internalized by Hela cells and accomplished a potent antitumor cell efficacy, indicating that the chitosan-based micelles might be an attractive new platform for efficient intracellular drug delivery.
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REACTIVE & FUNCTIONAL POLYMERS
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2012
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IF 2.479
Chunyan Liao,Junchao Huang,Shaofa Sun,Bo Xiao,Nuo Zhou,Dengke Yin,Ying Wan
Nerve growth factor (NGF)-loaded chitosan microspheres were prepared via emulsification method using sodium tripolyphosphate as a crosslinker. Some selected chitosan microspheres were embedded into chitosan–polycaprolactone (CH–PCL) multi-channel conduits that can potentially be used for long-gap nerve repair. PCL percentages in the CH–PCLs were optimized into a region changing from around 30 to 42 wt.% while the porosity and average channel diameter of the resulting multi-channel conduits were selected as about 80% and 200 μm, respectively. SEM images confirmed that the channels inside the conduits were longitudinally arrayed with an approximately parallel arrangement, and the NGF-loaded microspheres appeared to be embedded into the wall of channels without blocking. The compressive properties in wet state and in vitro degradation rates of CH–PCL multi-channel conduits were found to be mainly manipulated by the PCL content in the CH–PCLs whereas the cumulative amount of released NGF from the conduits could be independently regulated by altering the initial NGF load inside the embedded microspheres. The optimal microsphere-embedded CH–PCL multi-channel conduits with a dimension of around 6 mm in outer diameter and 30 mm in length were able to administrate bioactivity-preserved NGF release in a sustained and controlled manner without significant initial burst release, and the release rates of the conduits could be maintained with approximately linear characteristic over a period of time longer than 6 weeks.
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JOURNAL OF MATERIALS SCIENCE
·
2015
·Vol. 50
·期 14
·4914-4925
·
IF 2.371
Cheng Cui,Xia Dandan,Zhang Xiuli,Chen Li,Zhang Qiqing
The therapeutic concentration of cisplatin (CDDP) is usually associated with dose-limiting side effects. To avoid these harmful effects, a biocompatible hydrogel carrier which consisted of poly( N -isopropylacrylamide) and carboxymethyl chitosan was designed to deliver CDDP to the local environment of a solid tumor. The poly( N -isopropylacrylamide)-g-carboxymethyl chitosan hydrogels were synthesized by chemical crosslinking. Scanning electronic microscopy images showed that the hydrogels exhibited a cross-linked structure with the average pore size from 100 to 200 µm. Water contact angles and swelling studies suggested that the hydrogels had good hydrophilicity and the lower critical solution temperature lay in the vicinity of 32 °C. The MTT assays implied that the hydrogels were non-cytotoxic on NIH3T3 cells. In vitro release experiment demonstrated that the release of CDDP was controllable and sustained over a long period. Moreover, the released CDDP retained its anticancer activity on A549 cells. The hydrogels are promising carriers for sustained release of cisplatin.
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RSC Advances
·
2015
·Vol. 5
·期 86
·70109-70116
·
IF 3.84
Gongyan Liu,Quanqing Luo,Haibo Wang,Weihua Zhuang,Yunbing Wang
To realize desirable functions in the rather complex biological systems, a suitable surface coating is desirable for gold nanoparticles, which plays an important role in their colloidal stability and biocompatibility. In this work, a novel multidentate PEGylated chitosan derivative was synthesized by conjugating PEG and dithiolane lipoic acid (LA) to the chitosan backbone. Under reduction conditions, gold nanoparticles (AuNPs) could be in situ formed by the electrostatic interaction between amino groups of the chitosan derivative and gold chloride ions (AuCl4−), with their surface covalently coated by the multidentate PEGylated chitosan via the disulfide bond from LA. After the surface modification, such AuNPs exhibited remarkable colloidal stabilities under extreme conditions, including high salt conditions and complex biological media containing serum. Moreover, the multidentate PEGylated chitosan also provided AuNPs with good biocompatibility and low cytotoxicity, resistance of protein adsorption and anti-phagocytosis by RAW 264.7 cells. This kind of AuNP was expected to be a promising platform for applications in nanomedicine.
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MATERIALS RESEARCH BULLETIN
·
2015
·
IF 2.288
Dechao Shi,Fanyong Yan,Meng Wang,Yu Zou,Tancheng Zheng,Xuguang Zhou,Li Chen
In this paper, a novel fluorescent adsorbent (CS-RC) was developed for mercury(II) (Hg 2+ ) detection and removal by grafting a rhodamine derived probe onto the surface of chitosan. The UV–vis spectra and Fourier transform-infrared spectroscopy confirmed the successful loading of rhodamine derived probe. Compared with traditional chitosan adsorbents, this type of adsorbent not only showed extraordinary adsorption and removal ability for mercury ions, but served as an excellent colorimetric and fluorescence turn-on “naked-eye” sensor. The sensing performance suggested that the resulting adsorbent showed exclusively distinguish Hg 2+ from various metal ions and the linear response of fluorescence emission intensity to the concentration of Hg 2+ was obtained over a wide range of 0–6.0 μM with a detection limit of 3.42 × 10 −6 M. The adsorption and removal performance were also investigated and proved to be superior to pure chitosan. More importantly, this adsorbent still exhibited excellent adsorption performance after several regeneration cycles.
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BIOMACROMOLECULES
·
2015
·
IF 5.75
Xiaojie Song,Hao Wu,Shen Li,Yanfang Wang,Xiaojun Ma,Mingqian Tan
Nanocarriers play an important role in improving the photo- and thermal-stability of photosensitizers to gain better pharmacokinetics behavior in tumor photothermal therapy. Herein, PEGylated chitosan (CG-PEG; PEG: polyethylene glycol) nanoparticles with ultrasmall size (∼5 nm) were prepared through a water-in-oil reverse microemulsion method using genipin as a cross-linker. Particle size and zeta-potential can be tuned by varying the molar ratio between chitosan amino groups and genipin. CG-PEG-ICG (ICG: indocyanine green) nanoparticles were fabricated by adding ICG to CG-PEG aqueous solution through a self-assembly method via electrostatic interaction. The resultant CG-PEG-ICG nanoparticles exhibited improved photo- and thermal-stability, good biocompatibility, and low toxicity. When irradiated with a laser, the cells incubated with CG-PEG-ICG nanoparticles showed very low cell viability (15%), indicating the CG-PEG-ICG nanoparticles possess high in vitro photothermal toxicity. Moreover, the CG-PEG nanocarriers can significantly alter the biodistribution and prolong the retention time of ICG in the mice body after intravenous injection. In vivo photothermal study of tumors injected with CG-PEG-ICG nanoparticles containing ICG at a concentration greater than 100 μg·mL–1 (100 μL) induced irreversible tissue damage. The growth of U87 tumors was dramatically inhibited by CG-PEG-ICG nanoparticles, demonstrating that the CG-PEG nanoparticles may act as potential ICG nanocarriers for effective in vivo tumor photothermal therapy.
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MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Juan Chen,Liuqing Huang,Huixian Lai,Chenghao Lu,Ming Fang,Qiqing Zhang,Xuetao Luo
Cancer nanotherapeutics are rapidly progressing and being implemented to solve several limitations of conventional drug delivery systems. In this paper, we report a novel strategy of preparing methotrexate (MTX) nanoparticles based on chitosan (CS) and methoxypoly(ethylene glycol) (mPEG) used as nanocarriers to enhance their targeting and prolong blood circulation. MTX and mPEG-conjugated CS nanoparticles (NPs) were prepared and evaluated for their targeting efficiency and toxicity in vitro and in vivo. The MTX–mPEG–CS NP size determined by dynamic light scattering was 213 ± 2.0 nm with a narrow particle size distribution, and its loading content (LC %) and encapsulation efficiency (EE) were 44.19 ± 0.64% and 87.65 ± 0.79%, respectively. In vitro release behavior of MTX was investigated. In vivo optical imaging in mice proved that MTX was released from particles subsequently and targeted to tumor tissue, showing significantly prolonged retention and specific selectivity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay obviously indicated that the higher inhibition efficiency of MTX–mPEG–CS NPs meant that much more MTX was transferred into the tumor cells. A significant right-shift in the flow cytometry (FCM) assay demonstrated that MTX-loaded nanoparticles were far superior to a pure drug in the inhibition of growth and proliferation of Hela cells. These results suggest that MTX–mPEG–CS NPs could be a promising targeting anticancer chemotherapeutic agent, especially for cervical carcinoma.
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BIOMATERIALS
·
2014
·
IF 8.312
Xiaoying Wang,Yihang Chen,Fatima Zohra Dahmani,Lifang Yin,Jianping Zhou,Jing Yao
An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and synthesized for oral delivery of paclitaxel (PTX) to improve its oral bioavailability by increasing its water solubility and bypassing the P-gp drug efflux pumps . CQ conjugate had low critical micelle concentration (55.14 μg/mL), and could self assemble in aqueous condition to form polymeric micelles (PMs). PTX-loaded CQ PMs displayed a particle size of 185.8 ± 4.6 nm and polydispersity index (PDI) of 0.134 ± 0.056. The drug-loading content (DL) and entrapment efficiency (EE) were 33.62 ± 1.34% and 85.63 ± 1.26%, respectively. Moreover, PTX-loaded CQ PMs displayed similar sustained-release profile in simulated gastrointestinal fluids (pH 1.2/pH 6.8) and PBS (pH 7.4). In situ intestinal absorption experiment showed that PTX-loaded CQ PMs significantly improved the effective permeability of PTX as compared to verapamil ( P < 0.01). Likewise, PTX-loaded CQ PMs significantly enhanced the oral bioavailability of PTX, resulting in strong antitumor efficacy against tumor xenograft models with better safety profile as compared to Taxol ® and Taxol ® with verapamil. Overall, the results implicate that CQ PMs are promising vehicles for the oral delivery of water-insoluble anticancer drugs.
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POLYMER DEGRADATION AND STABILITY
·
2015
·
IF 3.163
Mingguang Li,Hongjun Zang,Jiaxuan Feng,Qing Yan,Nianqin Yu,Xiaolong Shi,Bowen Cheng
A new process for the efficient conversion of chitosan into 5-hydroxymethylfurfural (5-HMF) has been developed. Chitosan was hydrolyzed in the presence of acidic ionic liquids (ILs), with N-methyl imidazolium hydrogen sulfate ([MIM]HSO 4 ) giving the best results. The effects of reaction time, temperature and quantity of water and IL were investigated in detail. The optimal reaction conditions were found to be 4wt % IL ([MIM]HSO 4 ) aqueous solution under hydrothermal condition, 180 °C and a reaction time of 5 h. A yield of 29.5 mol% 5-HMF was obtained from 100 mg chitosan. Furthermore, chitosan with different molecular weight could be directly converted into 5-HMF in good yields under these conditions. More importantly, [MIM]HSO 4 could be recovered by simple post-processing and exhibited constant activity over 5 cycles.
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Marine Drugs
·
2017
·Vol. 15
·期 7
·223
·
IF 3.503
Na Li,Huanhuan Wang,Xiaosai Qu,Yu Chen
ROMP is an effective method for preparing functional polymers due to its having characteristics of “living” polymerization and rapid development of catalysts. In the present work, poly(norbornene-methylamine), a mimic of chitosan, was synthesized via ROMP reaction. The amino-protected product, 5-norbornene-2-(N-methyl)-phthalimide, was prepared by a reaction of 5-norbornene-2-methylamine with phthalic anhydride, which was then subjected to the ROMP reaction in the presence of Hoveyda-Grubbs 2nd catalyst to afford poly(norbornene-(N-methyl)-phthalimide). The target product, poly(norbornene-methylamine), was obtained by deprotection reaction of poly(norbornene-(N-methyl)-phthalimide). The products in each step were characterized by FTIR and1H-NMR, and their thermal stabilities were determined by TG analysis. The effects of molar ratio between monomer ([M]/[I]) and catalyst on the average relative molecular weight (Mn¯) and molecular weight distribution of the produced polymer products were determined by gel permeation chromatography (GPC). It was found that theMn¯of poly(norbornene-(N-methyl)-phthalimide) was controllable and exhibited a narrow polydispersity index (PDI) (~1.10). The synthesis condition of 5-norbornene-2-(N-methyl)-phthalimide was optimized by determining the yields at different reaction temperatures and reaction times. The highest yield was obtained at a reaction temperature of 130 °C and a reaction time of 20 min. Our work provides a new strategy to synthesize polymers with controllable structures and free –NH2groups via ROMP.Keywords:ROMP;poly(norbornene-methylamine);controllable;living polymerization;chitosan
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Guoxin Tan,Shihui Yu,Jinyu Li,Weisan Pan
This study aims to explore a novel composite thermosensitive in situ gelling formulation which the nanostructured lipid carriers (NLC) was incorporated into hydroxypropyltrimethyl ammonium chloride chitosan (HACC)-based hydrogels, and the resulting formulation investigated for its potential to act as a potential sustained ocular delivery system. NLC formulation loaded with dexamethasone (DXM) were prepared using the melt-emulsification method. The particle size, zeta potential , encapsulation efficiency, and morphological properties of the NLC were characterized. The HACC was synthesized and structure was analyzed by FT-IR and 1 H NMR . A thermosensitive hydrogel was designed and prepared by simply mixing HACC and β-glycerophosphate (β-GP). The obtained formulation showed a rapid solution-to-gel transition at 35 °C. The NLC were then incorporated in HACC/β-GP hydrogel to form a NLC-loaded hydrogel carrier. In vitro release studies, 88.65% of total DXM was released from the NLC-HACC/GP gel within 3 days, indicating DXM-based NLC-gel could release drug sustainably. Taken together, DXM-based NLC-HACC/GP gel is a promising drug delivery system.
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Oncotarget
·
2017
·
IF 5.168
Pengfei Chen,Sheng Mei,Chen Xia,Ren Zhu,Yichuan Pang,Jiying Wang,Jianfeng Zhang,Fangchun Shao,Shunwu Fan
The present study aimed to investigate the synergistic therapeutic effect of decreasing cartilage angiogenesis via exposure to crizotinib encapsulated by chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating crizotinib as a treatment for osteoarthritis. First, we developed and evaluated the characteristics of hydrogels and chitosan microspheres. Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1β in chondrocytes. Crizotinib ameliorated the pathological changes induced by interleukin-1β via its anti-angiogenesis function. In addition, we surgically induced osteoarthritis in mice, which were then injected intra-articularly with crizotinib-loaded biomaterials. Cartilage matrix degradation, expression of vascular endothelial growth factor and extracellular signal-regulated kinases 1/2 were evaluated after surgery. Treatment with the combination of crizotinib-loaded biomaterials retarded the progression of surgically induced osteoarthritis. Crizotinib ameliorated cartilage matrix degradation by promoting anti-angiogenesis and impeding extracellular signal-regulated kinases 1/2 signaling pathway. Our results demonstrate that the combination of photo-crosslinked hydrogel and crizotinib-loaded chitosan microspheres might represent a promising strategy for osteoarthritis treatment.
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