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使用小分子添加剂从水杨酸酯基聚(酸酐-酯)基质实现可调谐药物释放曲线

Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures.

作者信息

Ouimet Michelle A, Snyder Sabrina S, Uhrich Kathryn E

机构信息

Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA.

出版信息

J Bioact Compat Polym. 2012 Nov 1;27(6):540-549. doi: 10.1177/0883911512464605.

Abstract

Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory drug, chemically incorporated into the polymer backbone provide high inherent drug loading. These poly(anhydride-esters) hydrolytically degrade to release salicylic acid over extended time periods (>30 days); however, an initial lag period of no salicylic acid release is observed. This lag period could be unfavorable in applications where immediate salicylic acid release is desired. Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were admixed with various small molecules as a means to shorten or eliminate the lag period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures resulted in immediate salicylic acid release and a decrease in glass transition temperatures compared to polymer alone. By varying the amounts of salicylic acid and salicylic acid prodrugs incorporated into the polymer matrix, immediate and constant salicylic acid release profiles over varied time periods were achieved.

摘要

将非甾体抗炎药水杨酸化学结合到聚合物主链中的聚(酸酐 - 酯)具有高固有载药量。这些聚(酸酐 - 酯)通过水解降解在较长时间段(>30天)内释放水杨酸;然而,观察到存在一个无水杨酸释放的初始延迟期。在期望立即释放水杨酸的应用中,这个延迟期可能是不利的。将具有短(2天)和长(11天)延迟期的聚(酸酐 - 酯)与各种小分子混合,作为缩短或消除延迟期的一种方法。将水杨酸、更大的水杨酸前药以及两者的1:1组合进行物理混合,每种的含量分别为1%、5%和10%(w/w)。与单独的聚合物相比,所有混合物都导致水杨酸立即释放,并且玻璃化转变温度降低。通过改变掺入聚合物基质中的水杨酸和水杨酸前药的量,在不同时间段内实现了立即且持续的水杨酸释放曲线。

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