Blanco M Dolores, Sastre Roberto L, Teijón César, Olmo Rosa, Teijón José M
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Int J Pharm. 2006 Dec 1;326(1-2):139-47. doi: 10.1016/j.ijpharm.2006.07.030. Epub 2006 Jul 22.
Polymeric microsphere degradation must be taken into account in the design of drug delivery systems to be injected in in vivo systems, thus a prior analysis of in vitro degradation behaviour of microspheres appears to be necessary. In this study degradation characteristics of poly(lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) microspheres prepared by the spray-drying technique have been examined. It was found that a slow decrease in molecular weight took place during the first stage of degradation, and the value of the rate constant decreased with the increase of the percentage of lactic acid of the polymer in a linear way. Thus, the period of time of this first stage decreased with the increase of content of glycolidyl units of the polymer, and it was the unique stage observed in PLA microspheres after 5 months of study. During this period of time, significant mass loss was not observed in the microspheres. The second stage of degradation of PLGA microspheres showed a larger rate constant, whose value increased with the content of glycolidyl units of the polymer. Mass loss was observed from number-average molecular weight about 6000. A sharp decrease of glass transition temperature (T(g)) was observed coinciding with the start of mass loss. This fact was accompanied by a physical change of the samples, fusion of microspheres to form large particles, which also fusion to form a unique mass of polymer; moment from that the degradation process was quicker.
在设计用于体内注射的药物递送系统时，必须考虑聚合物微球的降解情况，因此对微球的体外降解行为进行预先分析似乎是必要的。在本研究中，对通过喷雾干燥技术制备的聚（丙交酯-共-乙交酯）（PLGA）和聚（D，L-丙交酯）（PLA）微球的降解特性进行了研究。结果发现，在降解的第一阶段分子量缓慢下降，并且速率常数的值随着聚合物中乳酸百分比的增加呈线性下降。因此，该第一阶段的时间随着聚合物中乙交酯单元含量的增加而减少，并且这是在研究5个月后在PLA微球中观察到的唯一阶段。在此期间，微球中未观察到明显的质量损失。PLGA微球降解的第二阶段显示出较大的速率常数，其值随着聚合物中乙交酯单元的含量而增加。从数均分子量约6000开始观察到质量损失。观察到玻璃化转变温度（T(g)）急剧下降，与质量损失的开始同时发生。这一事实伴随着样品的物理变化，微球融合形成大颗粒，这些大颗粒也融合形成聚合物的单一物质；从那时起降解过程更快。
