Department of Pharmacy, Faculty of Health and Medical Sciences , University of Copenhagen , Universitetsparken 2 , 2100 Copenhagen , Denmark.
Department of Food Science, Faculty of Science , University of Copenhagen , Rolighedsvej 26 , 1958 Frederiksberg C , Denmark.
ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36686-36692. doi: 10.1021/acsami.8b12475. Epub 2018 Oct 22.
Poly(lactic- co-glycolic acid) (PLGA) microparticles represent a promising formulation approach for providing steady pharmacokinetic/pharmacodynamic profiles of therapeutic drugs for a long period. Understanding and controlling the supramolecular structure of PLGA microparticles at a molecular level is a prerequisite for the rational design of well-controlled, reproducible sustained-release profiles. Herein, we reveal the role of PLGA molecular conformation in particle formation and drug release. The nanoscale network of PLGA microparticles spray-dried using the solvents with distinct polarities was investigated by using NMR and neutron scattering. By employing chemometric method, we further demonstrate the evolution of nanoscale networks in spray-dried PLGA microparticles upon water absorption. Our results indicate that PLGA molecules form more chain entanglements during spray drying when using the solvents with low polarity, where PLGA molecule adopts a more flexible, extended conformation, resulting in the network being more resistant to water absorption in spray-dried PLGA microparticles. This work underlines the role of PLGA molecular conformation in controlling formation and evolution of nanoscale network of spray-dried PLGA microparticles and will have important consequences in achieving customized drug release from the PLGA microparticles.
聚（丙交酯-共-乙交酯）（PLGA）微球是一种很有前途的制剂方法，可使治疗药物在很长一段时间内保持稳定的药代动力学/药效学特征。在分子水平上理解和控制 PLGA 微球的超分子结构是合理设计具有良好控制、可重复的缓释特征的前提。本文揭示了 PLGA 分子构象在颗粒形成和药物释放中的作用。采用具有不同极性的溶剂喷雾干燥的 PLGA 微球的纳米网络结构，通过 NMR 和中子散射进行了研究。通过采用化学计量学方法，我们进一步证明了在吸收水时喷雾干燥 PLGA 微球中纳米网络的演变。研究结果表明，当使用低极性溶剂进行喷雾干燥时，PLGA 分子会形成更多的链缠结，PLGA 分子呈现出更灵活、更伸展的构象，导致喷雾干燥 PLGA 微球中的网络更能抵抗水的吸收。这项工作强调了 PLGA 分子构象在控制喷雾干燥 PLGA 微球的纳米网络形成和演变中的作用，对实现从 PLGA 微球中定制药物释放具有重要意义。
