Properties of a peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods

Novel emulsion solvent diffusion methods in water or oil were developed to prepare the peptide (TRH and elcatonin)-loaded PLGA nanospheres, via the coprecipitation of drug and polymer in the emulsion droplets induced by the diffusion of solvent. The PLGA nanospheres prepared by the emulsion solvent diffusion method in water were unimodally dispersed particles with an average diameter of about 250 nm, whereas those prepared by the emulsion solvent diffusion method in oil and the phase separation method exhibited bimodal distribution with average diameter of about 700 and 800 nm, respectively. The content and recovery of the peptide and nanospheres prepared by the emulsion solvent diffusion method in oil were superior to those of nanospheres prepared using other methods. The drug release properties from nanospheres depended strongly on their preparation processes. The nanospheres prepared by the emulsion solvent diffusion method in oil, released the drug continuously over 14 days, the rate of which was determined by the diffusion of drug in the rigid matrix structure of the nanosphere. The drug release behavior of nanospheres prepared by the phase separation method exhibited a triphasic release pattern with an initial burst and an induction period followed by the diffusion of drug through the walls of the reservoir type nanospheres, which were produced via the phase separation of polymer deposited around the emulsion droplets of the drug. (C) 1998 Elsevier Science B.V.