<br>基于 PEG 和 PLA 共聚物共混物的药物递送系统的体外和体内水解降解行为,ACS Applied Materials & Interfaces

当前位置： X-MOL 学术 › ACS Appl. Mater. Interfaces › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

基于 PEG 和 PLA 共聚物共混物的药物递送系统的体外和体内水解降解行为
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-11-27 , DOI: 10.1021/acsami.2c13141
Feifei Ng ₁ , Victor Nicoulin ₁ , Charlotte Peloso ₁ , Silvio Curia ₁ , Joël Richard ₁ , Adolfo Lopez-Noriega ₁

Affiliation

本文介绍了 BEPO 的体外和体内降解情况，BEPO 是一种已上市的原位形成储库技术，用于配制长效注射剂。 BEPO 由聚（乙二醇）-嵌段-聚（乳酸）（PEG-PLA）三嵌段和二嵌段混合物在有机溶剂中的溶液组成，其中可以溶解或悬浮治疗剂。与水性环境接触后，溶剂扩散，聚合物沉淀，捕获药物并形成储库。对两种代表性的 BEPO 组合物进行了为期3 个月的体外降解研究，通过浸入 37°C 的磷酸盐缓冲盐水中，并在小型猪皮下注射后进行体内降解研究。通过储库重量损失确定的作为生物再吸收替代物的材料侵蚀率发生了很大变化，具体取决于测试项目内聚合物的组成和含量。结果表明，储库的溶胀特性和内部形态高度依赖于沉淀步骤期间的溶剂交换率。热分析显示，在降解过程中，储存库玻璃化转变温度有所增加，但在任何阶段都没有观察到结晶度。降解的储存库的化学成分通过¹ H NMR 和凝胶渗透色谱法测定，并证明均聚物（即游离 PLA 和 (m)PEG）富集，这对两种配方中的 (m)PEG-PLA 共聚物不利。据观察，储存库内降解剂的相对比例是由初始聚合物组合物驱动的。有趣的是，体外和体内结果显示出非常好的质量一致性。总而言之，本研究的结果表明，BEPO 组合物的不同水解降解行为可以通过调整配方的聚合物组成来调节。

"点击查看英文标题和摘要"

In Vitro and In Vivo Hydrolytic Degradation Behaviors of a Drug-Delivery System Based on the Blend of PEG and PLA Copolymers

This paper presents the in vitro and in vivo degradation of BEPO, a marketed in situ forming depot technology used for the formulation of long-acting injectables. BEPO is composed of a solution of a blend of poly(ethylene glycol)-block-poly(lactic acid) (PEG–PLA) triblock and diblock in an organic solvent, where a therapeutic agent may be dissolved or suspended. Upon contact with an aqueous environment, the solvent diffuses and the polymers precipitate, entrapping the drug and forming a reservoir. Two representative BEPO compositions were subjected to a 3-month degradation study in vitro by immersion in phosphate-buffered saline at 37 °C and in vivo after subcutaneous injection in minipig. The material erosion rate, as a surrogate of the bioresorption, determined via the depot weight loss, changed substantially, depending on the composition and content of polymers within the test item. The swelling properties and internal morphology of depots were shown to be highly dependent on the solvent exchange rate during the precipitation step. Thermal analyses displayed an increase of the depot glass transition temperature over the degradation process, with no crystallinity observed at any stage. The chemical composition of degraded depots was determined by ¹H NMR and gel permeation chromatography and demonstrated an enrichment in homopolymers, i.e., free PLA and (m)PEG, to the detriment of (m)PEG–PLA copolymers in both formulations. It was observed that the relative ratio of the degradants within the depot is driven by the initial polymer composition. Interestingly, in vitro and in vivo results showed very good qualitative consistency. Taken together, the outcomes from this study demonstrate that the different hydrolytic degradation behaviors of the BEPO compositions can be tuned by adjusting the polymer composition of the formulation.

更新日期：2023-11-27

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南