(93ae) Polyanhydride Microsphere Fabrication Methods for Protein Delivery: Which Method Is Superior?

When encapsulating proteins in polymeric microspheres for drug delivery there are three stages in which the stability of a protein is jeopardized: microsphere fabrication, storage, and release from the microsphere. This work investigated how different microsphere fabrication processes affected the stability and release kinetics of ovalbumin loaded into polyanhydride microspheres. Ovalbumin was encapsulated in microspheres made of poly(sebacic anhydride) (poly(SA)) and a 20:80 copolymer of poly [(1,6-bis-p-carboxyphenoxy)hexane] (poly(CPH))and poly (SA)). The microsphere fabrication methods used were: water/oil/water (w/o/w), water/oil/oil (w/o/o), solid/oil/oil (s/o/o), and a cryogenic atomization method. Ovalbumin release from poly(SA) and 20:80 (CPH:SA) microspheres was zero order and lasted ~3 and 6 weeks, respectively. When ovalbumin was encapsulated as a solid (s/o/o and cryogenic atomization method) larger initial bursts were seen. The primary structure of ovalbumin released form all microspheres was conserved as determined by SDS-PAGE. The secondary structure (determined by Fourier transform infrared spectroscopy (FTIR)) of ovalbumin encapsulated in the microspheres was conserved in all cases except for the 20:80 (CPH:SA) microspheres fabricated via the w/o/w method . In general, non-aqueous encapsulation methods are superior for protein stabilization.