2-羟丙基-β-环糊精配方对化疗 PLGA 纳米粒生物转运和递送的影响。

Effect of a 2-HP-β-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles.

机构信息

Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

Guangdong Provincial Engineering Center of Topical Precision Drug Delivery System, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Jun 17;15:2605-2618. doi: 10.2147/DDDT.S314361. eCollection 2021.

DOI:10.2147/DDDT.S314361

PMID:34168432

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8216700/

Abstract

BACKGROUND

The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles.

METHODS

PTX-loaded 2-HP-β-CD-modified PLGA nanoparticles (2-HP-β-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized.

RESULTS

Compared with the plain PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-β-CD/PLGA NPs was 2.4-fold higher than commercial Taxol and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-β-CD/PLGA NPs exhibited excellent stability in the circulation.

CONCLUSION

The results of this study suggest that the formulation that contains 2-HP-β-CD can prolong PTX release, enhance drug transport efficiency and serve as a potential tumor targeting system for PTX.

摘要

背景

本工作旨在利用 2-羟丙基-β-环糊精（2-HP-β-CD）的超分子作用，开发一种新的、可行的修饰策略，以提高载紫杉醇（PTX）聚乳酸-共-乙醇酸（PLGA）纳米粒的生物转运效率。

方法

采用改良乳液法制备载紫杉醇的 2-HP-β-CD 修饰的 PLGA 纳米粒（2-HP-β-CD/PLGA NPs）。然后对纳米粒的纳米特性、药物释放行为、体外细胞毒性、细胞摄取谱和体内生物行为进行了表征。

结果

与普通 PLGA NPs 相比，2-HP-β-CD/PLGA NPs 的粒径更小（151.03±1.36nm），包封效率更高（~49.12%的增加），药物释放更持久。当添加到 A549 人肺癌细胞中时，与 PLGA NPs 相比，2-HP-β-CD/PLGA NPs 在 MTT 测定中表现出更高的细胞毒性和改善的细胞摄取效率。药代动力学分析表明，2-HP-β-CD/PLGA NPs 的 AUC 值是商品 Taxol 的 2.4 倍，是普通 PLGA NPs 的 1.7 倍。在生物分布实验中，2-HP-β-CD/PLGA NPs 在循环中表现出良好的稳定性。