Eilleia Sarah Y, Soliman Mahmoud E, Mansour Samar, S Geneidi Ahmed
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Asian J Pharm Sci. 2018 Jul;13(4):297-309. doi: 10.1016/j.ajps.2018.03.003. Epub 2018 Apr 17.
The increasing demand for oral macromolecule delivery encouraged the development of microencapsulation technologies to protect such drugs against gastric and enzymatic degradation. However, microencapsulation often requires harsh conditions that may jeopardize their biological activity. Accordingly, many trials attempted to load macromolecules into porous drug carriers to bypass any formulation induced instability. In this study, we prepared chitosan coated porous poly (d, l-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with insulin using a novel loading technique; double freeze-drying. The results showed a significant increase in drug loading using only 5 mg/ml initial insulin concentration and conveyed a sustained drug release over uncoated MPs. Furthermore, SEM and confocal microscopy confirmed pore blocking and insulin accumulation within the MPs respectively. The oral pharmacodynamic data on rats also proved the preservation of insulin bioactivity after formulation. Finally, the new coating technique proved to be efficient in producing robust layer of chitosan with higher insulin loading while maintaining insulin activity.
对口服大分子递送的需求不断增加，促使微囊化技术得以发展，以保护此类药物免受胃酸和酶的降解。然而，微囊化通常需要苛刻的条件，这可能会损害其生物活性。因此，许多试验试图将大分子载入多孔药物载体，以规避任何由制剂引起的不稳定性。在本研究中，我们使用一种新型载入技术——双重冷冻干燥法，制备了载有胰岛素的壳聚糖包被多孔聚（d，l-丙交酯-共-乙交酯）（PLGA）微粒（MPs）。结果显示，仅使用5mg/ml的初始胰岛素浓度，载药量就显著增加，且与未包被的MPs相比，药物释放具有持续性。此外，扫描电子显微镜（SEM）和共聚焦显微镜分别证实了MPs内的孔隙堵塞和胰岛素蓄积。大鼠的口服药效学数据也证明了制剂后胰岛素生物活性得以保留。最后，新的包被技术被证明在产生具有更高胰岛素载量的坚固壳聚糖层同时保持胰岛素活性方面是有效的。
