Novel technique of insulin loading into porous carriers for oral delivery

摘要

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.