Preparation and characterization of protein C-loaded PLA nanoparticles

This paper deals with the preparation and the characterization of poly(lact ic acid) (PLA) nanoparticles containing protein C, a plasma inhibitor, Nano particles were prepared by the double emulsion method (w/o/w), using methyl ene chloride as an organic solvent and polyvinyl alcohol (PVA) or human ser um albumin (HSA) as a surfactant. The influence of experimental constraints such as sonication and organic solvent on protein C activity was evaluated . It appears that a short time of sonication as well as the addition of ace tone to methylene chloride (1/1) limited the lost of protein C activity. Th e study of protein C adsorption on blank PLA nanoparticles gave evidence to hydrophobic interactions between these two entities. The increase in PLA m olecular weight on the characteristics of the protein C-loaded nanoparticle s led to both a slightly decreased particle size and a lower polydispersity index, whereas the entrapment efficiency of protein C was not affected. Th e use of HSA as a surfactant allowed the increase in the entrapment efficie ncy of protein C but prevented its release. Finally, the evaluation of the activity of released protein C clearly illustrates that it was disturbed du ring the nanoparticle preparation. Thus, the obtained results emphasize the potential of protein C-loaded biodegradable nanoparticles for protein prog ressive delivery in plasma. (C) 1999 Elsevier Science B.V. All rights reser ved.