Biopolymer Particles for Proteins and Peptides Sustained Release Produced by Supercritical Emulsion Extraction

Abstract

In this work, biodegradable polymers have been successfully used to encapsulate proteins and peptides to prolong their therapeutic effect. Biodegradable microspheres prepared using poly(lactic acid), PLA, and its copolymers with poly(glycolic acid), PLGA, have been used as protein delivery systems. To overcome common limitation of the conventional emulsion/solvent removal techniques SC-CO2 has been proposed as extracting agent of the “oily” phase of emulsions, to lead to solvent-free microparticles. Supercritical emulsion extraction, produces an aqueous suspension of microparticles after the elimination of the organic solvent contained in the emulsion micelles. The process is very fast, due to the enhanced mass transfer of SC-CO2; the fast extraction rate results in a narrower particle size distribution (PSD) because droplets aggregation is minimized. The new proposed layout produces micro and submicrospheres in a robust and reproducible mode. The continuous process enhances the mass transfer due to a large contact area between SC-CO2 and emulsions in the tower, allowing the production of microspheres in short processing times and a higher throughput with smaller plant volumes eliminating the batch-to-batch repeatability problems. Biopolymer nanoparticles in the range 200-400nm and microparticles in the range 1-4μm encapsulating bovine serum albumin (BSA) as model protein and insulin like growth factor (h-IGF) were produced. The solvent of the oil phase was completely removed operating at 37°C and 100bar, preventing proteins from degradation.