Formulation and lyoprotection of poly(lactic acid-co-ethylene oxide) nanoparticles: Influence on physical stability and in vitro cell uptake

Purpose. To investigate the feasibility of producing freeze-dried poly (eth ylene oxide) (PEO)-surface modified nanoparticles and to study their abilit y to avoid the mononuclear phagocytic system (MPS), as a function of the PE O chain length and surface density. Methods. The nanoparticles were produced by the salting-out method using bl ends of poly(D,L-lactic acid) (PLA) and poly(D,L-lactic acid-co-ethylene ox ide) (PLA-PEO) copolymers. The nanoparticles were purified by cross-now fil tration and freeze-dried as such or with variable amounts of trehalose as a lyoprotectant. The redispersibility of the panicles was determined immedia tely after freeze-drying and after 12 months of storage at -25 degrees C. T he uptake: of the nanoparticles by human monocytes was studied in vitro, by now cytometry. Results. PLA-PEO nanoparticles could be produced from all the polymeric ble nds used. Particle aggregation after freeze-drying was shown to be directly related to the presence of PEG. Whereas this problem could be circumvented by use of trehalose, subsequent aggregation was shown to occur during stor age. These phenomena were possibly related to the specific thermal behaviou rs of PEO and trehalose. In cell studies, a clear relationship between the PEO content and the decrease of uptake was demonstrated. Conclusions. The rational design of freeze-dried PEG-surface modified nanop articles with potential MPS avoidance ability is feasible by using the poly mer blends approach combined with appropriate lyoprotection and optimal sto rage conditions.