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采用改良相转化法以无毒的丙二醇甲醚醋酸酯为聚合物溶剂制备聚乳酸-羟基乙酸共聚物微球

Preparation of PLGA Microspheres Using the Non-Toxic Glycofurol as Polymer Solvent by a Modified Phase Inversion Methodology.

作者信息

Sobel Douglas, Ramasubramanian Barath, Sawhney Puja, Parmar Keerat

机构信息

Medical School, Georgetown University, Washington, DC 20057, USA.

出版信息

Polymers (Basel). 2024 Feb 4;16(3):434. doi: 10.3390/polym16030434.

DOI:10.3390/polym16030434
PMID:38337323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10857302/
Abstract

Poly(D,L-lactide-co-glycolide is a biodegradable copolymer that can release pharmaceuticals. These pharmaceuticals can provide local therapy and also avert the clinical issues that occur when a drug must be given continuously and/or automatically. However, the drawbacks of using poly(D,L-lactide-co-glycolide include the kinetics and duration of time of poly(D,L-lactide-co-glycolide drug release, the denaturing of the drug loaded drug, and the potential clinical side effects. These drawbacks are mainly caused by the volatile organic solvents needed to prepare poly(D,L-lactide-co-glycolide spheres. Using the non-toxic solvent glycofurol solvent instead of volatile organic solvents to construct poly(D,L-lactide-co-glycolide microspheres may deter the issues of using volatile organic solvents. Up to now, preparation of such glycofurol spheres has previously met with limited success. We constructed dexamethasone laden poly(D,L-lactide-co-glycolide microspheres utilizing glycofurol as the solvent within a modified phase inversion methodology. These prepared microspheres have a higher drug load and a lower rate of water diffusion. This prolongs drug release compared to dichloromethane constructed spheres. The glycofurol-generated spheres are also not toxic to target cells as is the case for dichloromethane-constructed spheres. Further, glycofurol-constructed spheres do not denature the dexamethasone molecule and have kinetics of drug release that are more clinically advantageous, including a lower drug burst and a prolonged drug release.

摘要

聚（D，L-丙交酯-共-乙交酯）是一种可生物降解的共聚物，能够释放药物。这些药物可以提供局部治疗，还能避免在必须持续和/或自动给药时出现的临床问题。然而，使用聚（D，L-丙交酯-共-乙交酯）的缺点包括聚（D，L-丙交酯-共-乙交酯）药物释放的动力学和持续时间、载药药物的变性以及潜在的临床副作用。这些缺点主要是由制备聚（D，L-丙交酯-共-乙交酯）微球所需的挥发性有机溶剂引起的。使用无毒溶剂甘油甲缩醛代替挥发性有机溶剂来构建聚（D，L-丙交酯-共-乙交酯）微球可能会避免使用挥发性有机溶剂的问题。到目前为止，制备这种甘油甲缩醛微球以前取得的成功有限。我们在改进的相转化方法中利用甘油甲缩醛作为溶剂构建了载有地塞米松的聚（D，L-丙交酯-共-乙交酯）微球。这些制备的微球具有更高的载药量和更低的水扩散速率。与用二氯甲烷构建的微球相比，这延长了药物释放。甘油甲缩醛生成的微球对靶细胞也没有毒性，而二氯甲烷构建的微球则有毒性。此外，甘油甲缩醛构建的微球不会使地塞米松分子变性，并且具有在临床上更有利的药物释放动力学，包括更低的药物突释和更长的药物释放时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/4854d09c9768/polymers-16-00434-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/eab73c08f371/polymers-16-00434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/8fb61550a5a5/polymers-16-00434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/bd488d904756/polymers-16-00434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/f855f14488c0/polymers-16-00434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/d5dc6854c357/polymers-16-00434-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/d6498e3c8784/polymers-16-00434-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/608180a45d68/polymers-16-00434-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/78c7e6718c11/polymers-16-00434-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/a5fa914b407f/polymers-16-00434-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/4854d09c9768/polymers-16-00434-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/eab73c08f371/polymers-16-00434-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/8fb61550a5a5/polymers-16-00434-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/bd488d904756/polymers-16-00434-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/f855f14488c0/polymers-16-00434-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/d5dc6854c357/polymers-16-00434-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/d6498e3c8784/polymers-16-00434-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/608180a45d68/polymers-16-00434-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/78c7e6718c11/polymers-16-00434-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/a5fa914b407f/polymers-16-00434-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e764/10857302/4854d09c9768/polymers-16-00434-g010.jpg

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