Manoharan Chandrasekar, Singh Jagdish
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo 58105, USA.
J Pharm Sci. 2009 Feb;98(2):529-42. doi: 10.1002/jps.21445.
The purpose of this study was to investigate the effect of three zinc salts (i.e., zinc oxide, zinc carbonate, and zinc acetate) on insulin encapsulation efficiency (EE), stability, and in vitro release kinetics from poly(lactic-co-glycolic acid) (PLGA) microspheres. Microspheres were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique and characterized. Integrity of the encapsulated insulin and stability of the released insulin was assessed using a wide range of comprehensive analytical techniques. The EE of the formulation prepared without the addition of a zinc salt was 69%, the secondary structure of the encapsulated insulin in this formulation was found to be altered. Further, desamido insulin and aggregates were observed during in vitro release. When insulin was encapsulated with a zinc salt, EE increased significantly, secondary structure was unaltered, and no degradation or aggregation products were found. Initial burst release and release kinetics were markedly changed with the addition of zinc salts. More than 87% of the encapsulated insulin was released over a 2-week period with the addition of a zinc salt. In conclusion, zinc salts can be useful to increase the EE and stability of insulin in PLGA microspheres prepared by w/o/w technique.
本研究的目的是研究三种锌盐（即氧化锌、碳酸锌和醋酸锌）对胰岛素包封率（EE）、稳定性以及从聚乳酸-乙醇酸共聚物（PLGA）微球中的体外释放动力学的影响。通过水包油包水（w/o/w）双乳液溶剂蒸发技术制备微球并进行表征。使用多种综合分析技术评估包封胰岛素的完整性和释放胰岛素的稳定性。未添加锌盐制备的制剂的EE为69%，发现该制剂中包封胰岛素的二级结构发生了改变。此外，在体外释放过程中观察到脱酰胺胰岛素和聚集体。当胰岛素与锌盐一起包封时，EE显著增加，二级结构未改变，并且未发现降解或聚集产物。添加锌盐后，初始突释和释放动力学发生了显著变化。添加锌盐后，超过87%的包封胰岛素在2周内释放。总之，锌盐可用于提高通过w/o/w技术制备的PLGA微球中胰岛素的EE和稳定性。
