基于海藻酸盐的微凝胶的药物持续释放制备：体外和体内评价。

Fabrication of alginate based microgels for drug-sustained release: In-vitro and in-vivo evaluation.

机构信息

School of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung City 80708, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

School of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung City 80708, Taiwan.

出版信息

Int J Biol Macromol. 2021 Dec 1;192:958-966. doi: 10.1016/j.ijbiomac.2021.10.054. Epub 2021 Oct 14.

DOI:10.1016/j.ijbiomac.2021.10.054

PMID:34656537

Abstract

The current study was conducted to evaluate and analyze the effect of alginate, itaconic acid, and N,N'-methylene bisacrylamide in formulation of a novel alginate based microgels for sustained release of theophylline. The fabricated microgels were characterized by PXRD, SEM, FTIR, TGA and DSC respectively. FTIR revealed that alginate reacted with itaconic acid during polymerization reaction and confirmed the overlapping of itaconic acid on the backbone of alginate. TGA and DSC depicted high thermal stability of the fabricated microgels as compared to pure unreacted polymer and monomer. Likewise, dynamic swelling and percent drug release studies were carried out at different pH media i.e., pH 1.2, 4.6 and 7.4 respectively. Greater dynamic swelling and percent drug release was observed at higher pH 7.4 as compared to lower pH 4.6 and 1.2 due to the deprotonation of COOH groups of both alginate and itaconic acid respectively. The drug release mechanism from the fabricated microgels could be described by first order model. In-vivo pharmacokinetic study was performed on rabbits and exhibited sustained release in rabbits. Hence, the developed microgels indicated higher potential as the delivery system for the sustained delivery of theophylline.

摘要

本研究旨在评估和分析海藻酸钠、衣康酸和 N,N'-亚甲基双丙烯酰胺在新型海藻酸钠基微凝胶中的配方中的作用，用于茶碱的缓释。所制备的微凝胶分别通过 PXRD、SEM、FTIR、TGA 和 DSC 进行了表征。FTIR 表明海藻酸钠在聚合反应中与衣康酸反应，并证实了衣康酸在海藻酸钠主链上的重叠。TGA 和 DSC 表明与纯未反应的聚合物和单体相比，所制备的微凝胶具有更高的热稳定性。同样，在不同的 pH 介质（即 pH 1.2、4.6 和 7.4）下进行了动态溶胀和药物释放百分比研究。由于海藻酸钠和衣康酸的 COOH 基团分别去质子化，在较高 pH 7.4 时观察到较大的动态溶胀和药物释放百分比，而在较低 pH 4.6 和 1.2 时则较小。所制备的微凝胶的药物释放机制可以用一级模型来描述。在兔子体内进行了药代动力学研究，结果表明在兔子体内具有缓释作用。因此，所开发的微凝胶表明作为茶碱的缓释给药系统具有更高的潜力。