Protein C-loaded monomethoxypoly (ethylene oxide)-poly(lactic acid) nanoparticles

This paper deals with the preparation and characterization of monomethoxypo ly(ethylene oxide)-poly(lactic acid) (MPEO-PLA) nanoparticles containing pr otein C, a plasma inhibitor which regulates the mechanism of blood coagulat ion. Protein C was entrapped in MPEO-PLA nanoparticles using the double emu lsion method. The influence of MPEO-PLA copolymers on the different paramet ers was evaluated: characteristics of protein C-loaded nanoparticles, in vi tro release of the protein, evolution of the particle size with incubation time and MPEO release. The nanoparticle size does not depend on copolymer c haracteristics (MPEO and/or PLA block molecular weight). On the other hand, the efficiency of protein C entrapment is affected by the copolymer charac teristics. 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 tha t it is altered during its encapsulation. The optimization of the experimen tal parameters which disturbed entrapped protein C activity, i.e. sonicatio n time and organic solvent was investigated and has led to a preservation o f 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 pa rtially released which implicates further investigation for a potential the rapeutic use. (C) 2001 Elsevier Science B.V. All rights reserved.