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一种基于光聚合的半互穿聚合物网络水凝胶,结合了纳米颗粒,用于肿瘤的局部化疗。

A Photopolymerized Semi-Interpenetrating Polymer Networks-Based Hydrogel Incorporated with Nanoparticle for Local Chemotherapy of Tumors.

机构信息

Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhong-shan Road, Shanghai, 200062, People's Republic of China.

Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, China.

出版信息

Pharm Res. 2021 Apr;38(4):669-680. doi: 10.1007/s11095-021-03029-5. Epub 2021 Apr 1.

Abstract

PURPOSE

To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery.

METHODS

Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method.

RESULTS

The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice.

CONCLUSIONS

This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.

摘要

目的

为了解决肿瘤治疗中的局部药物递送问题,我们制备了一种新型的纳米粒子-水凝胶超结构,即由聚乙二醇二丙烯酸酯(PEGDA)和透明质酸(HA)组成的半互穿聚合物网络(semi-IPNs)水凝胶,并载入紫杉醇(PTX)负载的 PLGA 纳米粒子(PEGDA-HA/PLGA-PTX),通过原位紫外光聚合用于局部药物递送。

方法

以凝胶时间、溶胀率和降解率为指标,筛选并获得了制备水凝胶的最佳 Irgacure 2959 引发剂质量比和 HA 浓度。接下来,采用乳化溶剂蒸发法制备紫杉醇(PTX)负载的 PLGA 纳米粒子(PLGA-PTX NPs)。

结果

引发剂的质量比为 1%,PEGDA-HA 水凝胶的最佳 HA 浓度为 5mg/mL。体外实验表明,PLGA-PTX NPs 的细胞毒性与游离 PTX 相似,激光共聚焦显微镜和流式细胞术显示,NCI-H460 细胞的摄取率高达 96%。PEGDA-HA/PLGA-PTX 水凝胶局部药物递送系统的药物释放可持续 13 天。体内实验证明,PEGDAHA/PLGA-PTX 水凝胶能够有效抑制肿瘤生长,而不会在小鼠中引起毒性作用。

结论

本研究表明,PEGDA-HA/PLGA-PTX 水凝胶是一种很有前途的肿瘤治疗临床应用的局部药物递送系统。通过原位紫外光聚合制备了载紫杉醇纳米粒子的光聚合半互穿聚合物网络水凝胶,为肿瘤局部化疗提供了一种有前途的纳米平台。

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