Novel technique of insulin loading into porous carriers for oral delivery

The increasing demand for oral macromolecule delivery encouraged the development of mi-croencapsulation technologies to protect such drugs against gastric and enzymatic degra-dation. However, microencapsulation often requires harsh conditions that may jeopardizetheir biological activity. Accordingly, many trials attempted to load macromolecules intoporous drug carriers to bypass any formulation induced instability. In this study, we pre-pared chitosan coated porous poly(d, l-lactide-co-glycolide)(PLGA) microparticles(MPs)loaded with insulin using a novel loading technique; double freeze-drying. The resultsshowed a significant increase in drug loading using only 5 mg/ml initial insulin concen-tration and conveyed a sustained drug release over uncoated MPs. Furthermore, SEM andconfocal microscopy confirmed pore blocking and insulin accumulation within the MPs re-spectively. The oral pharmacodynamic data on rats also proved the preservation of insulinbioactivity after formulation. Finally, the new coating technique proved to be efficient inproducing robust layer of chitosan with higher insulin loading while maintaining insulinactivity.