University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
J Control Release. 2013 Mar 28;166(3):256-67. doi: 10.1016/j.jconrel.2012.12.024. Epub 2013 Jan 5.
Novel PLGA derivatives bearing carboxylated side chains have been synthesized and used to encapsulate the fragile drug apomorphine HCl with a solid-in-oil-in-water solvent extraction/evaporation method. Blends of d,l-lactide and l-3-(2-Benzyloxycarbonyl)Ethyl-1,4-Dioxane-2,5-dione (BED) were co-polymerized at different ratios via ring-opening using benzyl alcohol as initiator. Optionally, the ester groups in the side chains as well as the terminal ester groups were hydrogenolyzed (leading to free COOH groups). For reasons of comparison, different types of "conventional" PLGAs were also synthesized and used for apomorphine HCl encapsulation. The polymers and microparticles were thoroughly characterized using SEC, (1)H NMR, DSC, SEM, X-ray and laser diffraction, Headspace-GC as well as in vitro drug release measurements in flow-through cells and agitated flasks. Importantly, microparticles based on the new polymers bearing carboxylic groups in the polymeric side chains: (i) allowed a significant reduction of the amount of residual solvent (dichloromethane), and (ii) provided different types of drug release patterns compared to microparticles based on "conventional" PLGAs (at least partially due to altered polymer degradation kinetics). Thus, they offer an interesting potential as novel matrix formers in controlled drug delivery systems, overcoming potential shortcomings of standard PLGAs.
已经合成了具有羧基侧链的新型 PLGA 衍生物，并将其用于通过固-油-水溶剂萃取/蒸发法包封脆弱药物盐酸阿扑吗啡。通过使用苯甲醇作为引发剂开环，将 d,l-丙交酯和 l-3-(2-苄氧羰基)乙基-1,4-二氧六环-2,5-二酮（BED）的混合物以不同的比例共聚。可选地，侧链中的酯基以及末端酯基可以被氢化（生成游离的 COOH 基团）。出于比较的原因，还合成了不同类型的“常规”PLGA 并用于盐酸阿扑吗啡的包封。使用 SEC、（1）H NMR、DSC、SEM、X 射线和激光衍射、顶空-GC 以及在流动细胞和搅拌瓶中的体外药物释放测量，对聚合物和微球进行了彻底的表征。重要的是，基于具有聚合侧链中羧基的新型聚合物的微球：（i）允许显著减少残留溶剂（二氯甲烷）的量，（ii）与基于“常规”PLGA 的微球提供了不同类型的药物释放模式（至少部分归因于聚合物降解动力学的改变）。因此，它们作为新型控制药物释放系统中的基质形成剂具有很大的潜力，克服了标准 PLGA 的潜在缺点。
