PLASMA-PROTEIN ADSORPTION ON BIODEGRADABLE MICROSPHERES CONSISTING OFPOLY(D,L-LACTIDE-CO-GLYCOLIDE), POLY(L-LACTIDE) OR ABA TRIBLOCK COPOLYMERS CONTAINING POLY(OXYETHYLENE) - INFLUENCE OF PRODUCTION METHOD AND POLYMER COMPOSITION

Biodegradable particulate systems have been considered as parenteral d rug delivery systems. The adsorption of plasma proteins on micro- and nanoparticles is determined by the surface properties and may, in turn , strongly influence the biocompatibility and biodistribution of both carriers. In the present study the influence of the polymer compositio n and the production method of microspheres on the in vitro plasma pro tein adsorption were investigated using two-dimensional electrophoresi s (2-DE). Microparticles were prepared from poly(L-lactide) (L-PLA), p oly(D,L-lactide-co-glycolide) (PLGA), and ABA triblock copolymers cont aining hydrophilic poly(oxyethylene) (B-blocks) domains connected to h ydrophobic polyesters (A-blocks). Two different microencapsulation met hods were employed, namely the w/o/w emulsion solvent evaporation meth od and the spray-drying technique. It could be demonstrated that the p olymer composition and, especially, the encapsulation technique, influ enced the interactions with plasma proteins significantly. For example , the percentages of several apolipoproteins in the plasma protein ads orption patterns of spray-dried PLGA- and L-PLA-particles were distinc tly higher when compared to the adsorption patterns of the particles p roduced by the w/o/w-technique. Some adsorbed proteins were found to b e characteristic or even specific for particles produced by the same m ethod or consisting of identical polymers. Polyvinyl alcohol used as s tabilizer in the w/o/w-technique may decisively influence the surface properties relevant for protein adsorption. The plasma protein adsorpt ion on particles composed of ABA copolymers was drastically reduced wh en compared to microspheres made from pure polyesters. The adsorption patterns of ABA-particles were dominated by albumin. The plasma protei n adsorption patterns detected on the different microspheres are likel y to affect their in vivo performance as parenteral drug delivery syst ems. (C) 1998 Elsevier Science B.V. All rights reserved.