BIODEGRADABLE SUBMICRON CARRIERS FOR PEPTIDE DRUGS - PREPARATION OF DL-LACTIDE/GLYCOLIDE COPOLYMER (PLGA) NANOSPHERES WITH NAFARELIN ACETATE BY A NOVEL EMULSION-PHASE SEPARATION METHOD IN AN OIL SYSTEM

PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (nafarelin acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers: The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500-800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.