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 biodegradable and well tolerated colloidal suspensions. Solvent evaporation and microfluidisation did not damage the albumin molecules; therefore, PLA/albumin nanoparticles are no more immunogenic than native albumin in solution. However, rapid albumin exchanges on the nanoparticle surface probably does not prevent C3-complement binding and phagocytosis by the liver Kupffer cells. Because of their possible intracellular accumulation 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 copolymer. The oriented PEG layer, coating the nanoparticle surface, dramatically increases the plasma half-life of the colloidal carrier ('stealth nanoparticles'). In this way, the PLAPEG nanoparticle half-life is about 6 h instead of a few minutes as for PLA/albumin or PLA/poloxamer 188-coated nanoparticles. The plasma clearance of a water-insoluble hydrophobic drug encapsulated in stealth nanoparticles and administered intravenously, decreases very significantly in comparison with non-stealth nanoparticles. PLAPEG nanoparticles can be considered as a sustained release parenteral (intravenous) dosage form.