Protein C-loaded monomethoxypoly (ethylene oxide)-poly(lactic acid) nanoparticles.
This paper deals with the preparation and characterization of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO-PLA) nanoparticles containing protein C, a plasma inhibitor which regulates the mechanism of blood coagulation. Protein C was entrapped in MPEO-PLA nanoparticles using the double emulsion method. The influence of MPEO-PLA copolymers on the different parameters was evaluated: characteristics of protein C-loaded nanoparticles, in vitro release of the protein, evolution of the particle size with incubation time and MPEO release. The nanoparticle size does not depend on copolymer characteristics (MPEO and/or PLA block molecular weight). On the other hand, the efficiency of protein C entrapment is affected by the copolymer characteristics. The burst effect during the protein C release is increased with the hydrophilic character of the copolymer. Moreover, protein C adsorption on the particle surface during its release may be related to MPEO release. Only 25% of the released protein C is active, which clearly illustrates that it is altered during its encapsulation. The optimization of the experimental parameters which disturbed entrapped protein C activity, i.e. sonication time and organic solvent was investigated and has led to a preservation of protein C activity. Then, to optimize its entrapment efficiency, a blend PLA/MPEO-PLA (25/75) was used to prepare nanoparticles. This blend limited burst effect of protein C and its adsorption. However, protein C is only partially released which implicates further investigation for a potential therapeutic use.
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
D007773:Lactates / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011486:Protein C / Q000008:administration & dosage* / Q000737:chemistry
D007773:Lactates; D011108:Polymers; D011486:Protein C; C058523:polyethylene oxide-polylactic acid block copolymer; D011092:Polyethylene Glycols