Abstract: The invention provides a novel submicron system for the oral administration of proteins. An effective oral carrier for proteins should shield its content against the gastrointestinal tract proteases and be capable of facilitating the uptake of the protein drug across the gastrointestinal epithelium. The present invention relates to production of gelled particles which comprises a protein drug susceptible to enzymatic degradation by enzymes and acid conditions in the stomach, a polymeric matrix which undergoes precipitation-swelling process, and two-layer-coating materials which are themselves capable of enhancing absorption of said drug across the intestinal mucosal tissues and of inbihiting degradation of said drug by gastric enzymes. Insulin-loaded particles with appropriate submicron size for gastrointestinal absorption were made of natural occurring polymers by emulsification-based method and proved to be gastric pH and protease protective.

Abstract: The present invention describes a method to encapsulate bioactive macromolecules, as example but not limited for, peptidic drugs, into polymeric particles sizing less than 10 ?m of diameter Particle production is based on emulsification/internal gelation procedure and comprises a formation of a water-in-oil emulsion followed by solubilization of dispersed insoluble calcium complex triggering gelation of said polymer dispersed in internal phase, by ionic cross-linking with free calcium ions. Finally, resulting gelled particles dispersed in the oil phase are recovered by partition phases coupled with high speed centrifugation cycles. In this case, the present invention describes a precise methodology to recover said gelled polymeric particles after particle production and includes an addition of acetate buffer solution at predetermined pH, dehydrating agents and residual oil dissolvent agent, at predetermined concentration, followed by high speed centrifugation cycles.