Development and characterization of protein-loaded poly(lactide-co-glycolide) nanospheres

The goal of this work is to develop poly(lactide-co-glycolide) (PLGA) nanospheres designed to deliver proteins for extended periods of time. To accomplish this goal a water-in-oil-in-water emulsion technique was conveniently modified. A study was performed to evaluate how the solvent elimination procedure, the copolymer type (different molecular weight and containing either free or esterified carboxyls) and the surfactant Poloxamer 188 affected the properties of the nanoparticles. The size of the nanospheres become larger (from 300 to 600 nm) by increasing the copolymer molecular weight and by the incorporation of Poloxamer 188. The protein loading efficiency varied from 40 to 90%, reaching the maximum Values for the formulations made of PLGA with free carboxyls. However, the co-encapsulation of Poloxamer 188 reduced the protein loading. The in vitro protein release rate, was fairly constant after an initial burst release. The release rate was significantly reduced for the copolymer with terminal free carboxyls but was enhanced by the incorporation of Poloxamer 188 in the nanoparticles. No significant aggregation or fragmentation of the encapsulated protein was observed after incubation for 1 month. Consequently, these nanoparticles can be proposed as new controlled release protein delivery systems. (C) 1997 Elsevier Science B.V.