Synthesis and Degradation of Biodegradable Polyanhydride Microspheres for Encapsulation of Proteins.

Abstract

A new biodegradable polyanhydride copolymer, poly[bis(p-carboxyphenoxy)butane-sebacic acid] [poly(CPB:SA)], was synthesised using modified melt polycondensation. Microspheres made using the new polyanhydride copolymers were prepared using a modified double emulsion, solvent evaporation technique using a model protein, bovine serum albumin (BSA) at a 10% w/w theoretical load. The degradation studies of the polymers and microspheres were carried out in PBS, with shaking, at 37°C and monitored using gel permeation chromatography (GPC), IR spectroscopy and scanning electron microscopy (SEM). Water penetration and anhydride bond cleavage (polymer degradation) occurred rapidly (< 5 days) compared to the time scale of overall microsphere erosion (weeks to months) with different polymer compositions. Subsequent to bond cleavage, the ultimate erosion of the microsphere and release of entrapped BSA was due mainly to the slow dissolution of the individual hydrophobic monomers (CPB and SA) from the microsphere surface. This surface erosion mechanism leads to predictable drug release rates which may be appropriate for the delivery of many protein therapeutics, especially vaccine antigens. Protein release rates could be adjusted by changing monomer composition ratios. Due to the fast degradation of anhydride bonds relative to microsphere erosion, initial polymer molecular weight did not have a significant effect on macromolecule release rates. Instead, protein release rates from polymers of identical composition could be varied by changing the amount of protein encapsulated.