Preparation and characterization of protein C-loaded PLA nanoparticles.
This paper deals with the preparation and the characterization of poly(lactic acid) (PLA) nanoparticles containing protein C, a plasma inhibitor. Nanoparticles were prepared by the double emulsion method (w/o/w), using methylene chloride as an organic solvent and polyvinyl alcohol (PVA) or human serum 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 acetone to methylene chloride (1/1) limited the lost of protein C activity. The study of protein C adsorption on blank PLA nanoparticles gave evidence to hydrophobic interactions between these two entities. The increase in PLA molecular weight on the characteristics of the protein C-loaded nanoparticles led to both a slightly decreased particle size and a lower polydispersity index, whereas the entrapment efficiency of protein C was not affected. The use of HSA as a surfactant allowed the increase in the entrapment efficiency of protein C but prevented its release. Finally, the evaluation of the activity of released protein C clearly illustrates that it was disturbed during the nanoparticle preparation. Thus, the obtained results emphasize the potential of protein C-loaded biodegradable nanoparticles for protein progressive delivery in plasma.
Zambaux
M F
MF
Laboratoire d'Hématologie-Physiologie, Faculté de Pharmacie, 5, rue Albert Lebrun, 54001, Nancy Cedex, France.
Bonneaux
F
F
Gref
R
R
Dellacherie
E
E
Vigneron
C
C
D000925:Anticoagulants / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D004355:Drug Stability; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry*; D008752:Methylene Chloride / Q000737:chemistry; D008863:Microspheres; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011486:Protein C / Q000737:chemistry*; D013010:Sonication; D013501:Surface-Active Agents / Q000737:chemistry
D000925:Anticoagulants; D003692:Delayed-Action Preparations; D011108:Polymers; D011486:Protein C; D013501:Surface-Active Agents; D019344:Lactic Acid; D008752:Methylene Chloride; D011142:Polyvinyl Alcohol