Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Am Chem Soc. 2012 Oct 3;134(39):16352-9. doi: 10.1021/ja306866w. Epub 2012 Sep 21.
The effect of sequence on copolymer properties is rarely studied despite the precedent from Nature that monomer order can create materials of significant diversity. Poly(lactic-co-glycolic acid) (PLGA), one of the most important biodegradable copolymers, is widely used in an unsequenced, random form for both drug delivery microparticles and tissue engineering matrices. Sequenced PLGA copolymers have been synthesized and fabricated into microparticles to study how their hydrolysis rates compare to those of random copolymers. Sequenced PLGA microparticles were found to degrade at slower, and often more constant, rates than random copolymers with the same lactic to glycolic acid ratios as demonstrated by molecular weight decrease, lactic acid release, and thermal property analyses. The impact of copolymer sequence on in vitro release was studied using PLGA microparticles loaded with model agent rhodamine-B. These assays established that copolymer sequence affects the rate of release and that a more gradual burst release can be achieved using sequenced copolymers compared to a random control.
尽管自然界已经证明单体顺序可以创造出具有显著多样性的材料，但序列对共聚物性质的影响却很少得到研究。聚（乳酸-共-乙醇酸）（PLGA）是最重要的生物可降解共聚物之一，广泛以未排序的随机形式用于药物输送微球和组织工程基质。已经合成了序列 PLGA 共聚物并将其制成微球，以研究它们的水解速率与随机共聚物的水解速率相比如何。通过分子量降低、乳酸释放和热性能分析表明，与具有相同乳酸-乙醇酸比的随机共聚物相比，序列 PLGA 微球的降解速度更慢，而且通常更稳定。通过装载模型药物罗丹明 B 的 PLGA 微球研究了共聚物序列对体外释放的影响。这些实验确定了共聚物序列会影响释放速率，并且与随机对照相比，使用序列共聚物可以实现更渐进的爆发式释放。
