In vitro drug release behavior of D,L-lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method.
Nanospheres with D,L-lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion method. Nafarelin acetate (NA), a luteinizing hormone-releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone-dichloromethane-water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200-300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of the rapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water-soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug-release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found tht the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the porous matrix structure.(ABSTRACT TRUNCATED AT 250 WORDS)
Niwa
T
T
Department of Pharmaceutical Engineering, Gifu Pharmaceutical University, Japan.
Takeuchi
H
H
Hino
T
T
Kunou
N
N
Kawashima
Y
Y
D000284:Administration, Oral; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002627:Chemistry, Physical; D004058:Diffusion; D004355:Drug Stability; D004655:Emulsions; D005750:Gastric Juice / Q000378:metabolism; D019344:Lactic Acid; D008832:Microchemistry; D008863:Microspheres; D017274:Nafarelin / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D012997:Solvents; D013499:Surface Properties
D004655:Emulsions; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017274:Nafarelin; D011100:Polyglycolic Acid; D019344:Lactic Acid