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51.
Juan Wu Yueqing Shen Wei Jiang Yewen Shen 《Journal of biomaterials science. Polymer edition》2016,27(13):1303-1316
Targeted and efficient delivery of drug to tumor is one of the crucial issues in cancer therapy. In this work, we have successfully designed and prepared the pH-sensitive magnetic nanoparticles (MNPs) as targeted anticancer drug carriers, in which the MNPs were coated by poly(acrylic acid) (PAA) and the obtained PAA@MNPs exhibited a size within 100 nm, good stability, and superparamagnetic responsibility (Ms 45.97 emu/g). Doxorubicin (DOX) can be successfully loaded onto MNPs via electrostatic interaction, and the drug loading content and loading efficiency are 26.4 and 88.1%, respectively. Moreover, the release studies showed that the drug-loaded carriers (MNPs-DOX) had excellent pH sensitivity, 75.6% of the loaded DOX was released at pH 4.0 within 48 h. Importantly, MTT assays in HUVEC and MCF-7 cells demonstrated that MNPs-DOX exhibited high anti-tumor activity, while the PAA@MNPs were practically nontoxic. Thus, our results revealed that PAA@MNPs would be a competitive candidate for biomedical application and MNPs-DOX could be used in targeted cancer therapy. 相似文献
52.
Purpose Dynamic PEG-polycation copolymers that release PEG and degrade into small fragments after cell entry might present efficient
and biocompatible gene carriers.
Methods PEG-OEI-MK was synthesized by copolymerization of 5 kDa polyethyleneglycol (PEG) and 800 Da oligoethylenimines through acid-degradable
acetone-bis-(N-maleimidoethyl)ketal linkers (MK). To evaluate any benefit of the reversible over stable linkage, also the corresponding
pH-stable analog, PEG-OEI-BM, was synthesized via ether linkages. Luciferase and GFP expression plasmids were used for transfections, in vivo biocompatibility was evaluated by intravenous application of polymers in Balb/c mice.
Results PEG-OEI-MK showed efficient DNA binding as analyzed by ethidium bromide exclusion, resulting in formation of polyplexes with
sizes around 100 nm and surface charges of below 5 mV zeta potential. This surface shielding of PEG-OEI-MK polyplexes remained
stable at neutral pH 7.4, while polyplexes deshielded and aggregated at pH 5 within 15–30 min. Cell culture experiments demonstrated
reduced polymer toxicity compared to the non-PEGylated OEI-MK. Transfection experiments demonstrated reduced gene expression
of PEG-OEI-BM compared with the non-PEGylated analog OEI-BM, whereas the pH-reversible polymer PEG-OEI-MK mediated a significant
increased transfection efficiency over the non-PEGylated OEI-MK.
Conclusions PEG-OEI-MK mediated the highest gene transfer at lowest cytotoxicity levels and also best in vivo biocompatibility. 相似文献
53.
Preparation and characterization of dual pH-sensitive polymer-doxorubicin conjugate micelles
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Yang Zou Yao Jin Yuanhang Zhou Chuyu He Yunqiang Deng Shidi Han Chuhang Zhou Xinru Li Yanxia Zhou Yan Liu 《中国药学》2018,27(8):530-539
In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) with doxorubicin (PEOz-PLA-imi-DOX) to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLAvia acid cleavable benzoic imine linker and characterized by 1H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be (14.84±3.85) mg/L. The conjugate micelles (denoted as PP-DOX-PM) formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles’ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth. 相似文献
54.
Zhe Wang Xiangping Deng Jinsong Ding Wenhu Zhou Xing Zheng Guotao Tang 《International journal of pharmaceutics》2018,535(1-2):253-260
During the past decades, chemotherapy has been regarded as the most effective method for tumor therapy, but still faces significant challenges, such as poor tumor selectivity and multidrug resistance. The development of targeted drug delivery systems brings certain dramatic advantages for reducing the side effects and improving the therapeutic efficacy. Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for targeted therapy. Among these approaches, pH-sensitive micelles are regarded as the most general strategy with advantages of increasing solubility of water-insoluble drugs, pH-sensitive release, high drug loading, etc.This review will focus on the potential of pH-sensitive micelles in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations. Sufficient understanding of these mechanisms will help us to design more efficient pH-sensitive drug delivery system to address the challenges encountered in targeted drug delivery systems for tumor therapy. 相似文献
55.
Treatment of cervical cancer by siRNA-loaded chitosan-coated calcium phosphate nanoparticles
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In the present study, a chitosan-coated calcium phosphate nanoparticle (CS/CaP/siRNA NP) was developed to deliver siRNA for treatment of cervical cancer. The CS/CaP/siRNA NPs were prepared by the nano-precipitation method. The resulted NPs had a uniform spherical morphology with a size of ~194 nm and a zeta potential of ~+27 mV. In vitro experiments demonstrated that these NPs could efficiently deliver siEGFR into Hela cells and significantly down-regulate the EGFR expression level, which was probably associated with enhanced cell adhesion of chitosan, leading to extended residence time of cell internalization. Then the internalized CS/CaP/siRNA NPs exhibited pH-responsive disassembly of NPs, resulting in the enhanced release of siRNA and rapid lysosomal escape into cytoplasm. Moreover, in vivo anticancer results showed that the CS/CaP/siRNA NPs had significant inhibitory effects on tumor growth after intratumoral injection in Hela tumor xenografted nude mice, accompanying with no obvious changes of body weight during the whole experimental period. All these results indicated that the CS/CaP/siRNA NPs would have great potential to deliver siRNA for the treatment of cervical cancer via mucosal administration. 相似文献
56.
Saeed Ghanbarzadeh Arash Khorrami Leila Mohamed Khosroshahi 《Pharmaceutical biology》2014,52(7):848-854
Context: Liposomes are increasingly employed to deliver chemotherapeutic agents, antisense oligonucleotides, and genes to various therapeutic targets.Objective: The present investigation evaluates the ability of fusogenic pH-sensitive liposomes of rapamycin in increasing its antiproliferative effect on human breast adenocarcinoma (MCF-7) cell line.Materials and methods: Cholesterol (Chol) and dipalmitoylphosphatidylcholine (DPPC) (DPPC:Chol, 7:3) were used to prepare conventional rapamycin liposomes by a modified ethanol injection method. Dioleoylphosphatidylethanolamine (DOPE) was used to produce fusogenic and pH-sensitive properties in liposomes simultaneously (DPPC:Chol:DOPE, 7:3:4.2). The prepared liposomes were characterized by their size, zeta potential, encapsulation efficiency percent (EE%), and chemical stability during 6 months. The antiproliferative effects of both types of rapamycin liposomes (10, 25, and 50?nmol/L) with optimized formulations were assessed on MCF-7 cells, as cancerous cells, and human umbilical vein endothelial cells (HUVEC), as healthy cells, employing the diphenyltetrazolium bromide (MTT) assay for 72?h.Results and discussion: The particle size, zeta potential, and EE% of the liposomes were 165?±?12.3 and 178?±?15.4?nm, ?39.6?±?1.3, and ?41.2?±?2.1?mV as well as 76.9?±?2.6 and 76.9?±?2.6% in conventional and fusogenic pH-sensitive liposomes, respectively. Physicochemical stability results indicated that both liposome types were relatively stable at 4?°C than 25?°C. In vitro antiproliferative evaluation showed that fusogenic pH-sensitive liposomes had better antiproliferative effects on MCF-7 cells compared to the conventional liposomes. Conversely, fusogenic pH-sensitive liposomes had less cytotoxicity on HUVEC cell line. 相似文献
57.
目的由于在治疗肠道或某些全身性疾病中具有特殊的优点,口服结肠靶向给药系统受到更多的关注。但消化道的复杂性导致影响药物在结肠靶向释药的因素较多,重现性不好。本文对经口服药物结肠靶向释药的生理因素、目前已有的制备技术及应用进行综述。 相似文献
58.
59.
目的 基于羧甲基壳聚糖(carboxymethyl chitosan,CMC)-氧化透明质酸(oxidized hyaluronic acid,OHA)的自组装行为,构建一种用于局部递送难溶性药物的pH响应型纳米乳水凝胶给药系统。方法 采用自乳化法制备丹参酮ⅡA(tanshinoneⅡA,TanⅡA)纳米乳,通过平衡溶解度的考察和伪三元相图的绘制优化纳米乳处方,对纳米乳进行理化性质考察。高碘酸钠氧化法制备OHA,以成胶时间为指标优选CMC和OHA的浓度。将OHA溶解于纳米乳中与CMC溶液自组装形成Tan ⅡA纳米乳水凝胶(CMC-OHA/Tan ⅡA-NBHs)。对得到的CMC-OHA/Tan ⅡA-NBHs进行理化性质和体外抑菌活性评价。结果 优化处方可制备得到O/W型Tan ⅡA纳米乳,粒径为(52.18±0.15)nm,PDI为0.165±0.012。自组装得到的CMC-OHA/TanⅡA-NBHs具有良好... 相似文献
60.
This study primarily focused on the anti-metastatic activity of doxorubicin (DOX) loaded in a pH-sensitive mixed polymeric micelle formed from two block polymers: poly(l-lactide) (PLLA) (Mn 3000)-b-poly(ethylene glycol) (PEG) (Mn 2000)-folate and poly(l-histidine) (PHis) (Mn 4700)-b-PEG (Mn 2000). Tumor formation and metastasis in mice were examined using a murine mammary carcinoma cell of 4T1 which is one of the most aggressive metastatic cancer cell lines. The efficacy was evaluated by tumor size, body weight change, survival rate, dorsal skin fold window chamber model, and histological observation of the lung, heart, liver and spleen after treatment with various DOX formulations. When the tumor reached 50-100 mm3 in size, the mice were treated 4 times at a 3-day interval at a dose of 10 mg DOX/kg. The mixed micelle formulation resulted in retarded tumor growth, no weight loss, and no death for 4-5 weeks. In another set of the in vivo test for histological evaluation of the organs, the mice were similarly treated but the formulations were injected one day after 4T1 cell inoculation. The treatment by DOX loaded mixed micelle showed no apparent metastasis till 28 days. However, significant metastasis to the lung and heart was observed on Day 28 when the mice were treated with DOX carried by PBS, PLLA-b-PEG micelle and PHis-b-PEG micelle. 相似文献