NON-STEALTH (POLY(LACTIC ACID ALBUMIN)) AND STEALTH (POLY(LACTIC ACID-POLYETHYLENE GLYCOL)) NANOPARTICLES AS INJECTABLE DRUG CARRIERS

Stealth liposomes and, today, stealth nanoparticles, constitute a new generation of parenteral therapeutic systems. PLA/abumin nanoparticles are of particular interest because they constitute fully biodegradabl e and well tolerated colloidal suspensions. Solvent evaporation and mi crofluidisation did not damage the albumin molecules; therefore, PLA/a lbumin nanoparticles are no more immunogenic than native albumin in so lution. However, rapid albumin exchanges on the nanoparticle surface p robably does not prevent C3-complement binding and phagocytosis by the liver Kupffer cells. Because of their possible intracellular accumula tion and toxicity, PLA/albumin nanoparticles are presumably limited to subcutaneous or intramuscular administration. Poly(D,L-lactide)-poly( ethylene glycol) (PLA-PEG) is a new biodegradable hydrophobic dibloc c opolymer. The oriented PEG layer, coating the nanoparticle surface, dr amatically increases the plasma half-life of the colloidal carrier ('s tealth nanoparticles'). In this way, the PLAPEG nanoparticle half-life is about 6 h instead of a few minutes as for PLA/albumin or PLA/polox amer 188-coated nanoparticles. The plasma clearance of a water-insolub le hydrophobic drug encapsulated in stealth nanoparticles and administ ered intravenously, decreases very significantly in comparison with no n-stealth nanoparticles. PLAPEG nanoparticles can be considered as a s ustained release parenteral (intravenous) dosage form.