Protein micro and nanoencapsulation within glycol-chitosan/Ca2+/alginate matrix by spray drying

Abstract

Encapsulation of therapeutic peptides and proteins into polymeric micro and nanoparticulates has been proposed as a strategy to overcome limitations to oral protein administration. Particles having diameter less than 5 µm are able to be taken up by the M cells of Peyer’s patches found in intestinal mucosa. Current formulation methodologies involve organic solvents and several time consuming steps. In this study, spray drying was investigated to produce protein loaded micro/nanoparticles, as it offers the potential for single step operation, producing dry active-loaded particles within the micro to nano-range. Spherical, smooth surfaced particles were produced from alginate/protein feed solutions. The effect of operational parameters on particle properties such as recovery, residual activity and particle size was studied using subtilisin as model protein. Particle recovery depended on the inlet temperature of the drying air, and mean particle size ranged from 2.2 to 4.5 µm, affected by the feed rate and the alginate concentration in the feed solution. Increase in alginate:protein ratio increased protein stability. Presence of 0.2 g trehalose/g particle increased the residual activity up to 90%. Glycol-chitosan-Ca2+alginate particles were produced in a single step operation, with resulting mean diameter of 3.5 μm. Particles showed fluorescein isothiocyanate labeled bovine serum albumin (BSA)-protein entrapment with increasing concentration toward the particle surface. Similar, limited release profiles of BSA, subtilisin and lysozyme were observed in gastric simulation, with ultimate full release of the proteins in gastrointestinal simulation.