title: Conjugation of drug to poly(D,L-lactic-co-glycolic acid) for controlled release from biodegradable microspheres.
abstract: Poly(d,l-lactic-co-glycolic acid) (PLGA) was chemically conjugated to a model drug, N-(9-fluorenylmethoxycarbonyl-N-tert-butoxycarbonyl-l-tryptophan (Fmoc-Trp(Boc)) via an ester linkage. Various coupling reaction conditions were tested to optimize the conjugation process between a hydroxyl terminal group of PLGA and a carboxylic acid group of Fmoc-Trp(Boc). Two different lactic/glycolic acid compositions of PLGA (50/50 and 75/25) were used for the conjugation. The Fmoc-Trp(Boc)-PLGA conjugates were formulated into microspheres by a solvent evaporation technique for controlled release of Fmoc-Trp(Boc) over an one month period. A linear constant release of Fmoc-Trp(Boc) and its water-soluble PLGA oligomer conjugates was observed over an extended period without any initial burst effect, while unconjugated Fmoc-Trp(Boc) encapsulated within microspheres exhibited a rapid release profile. In addition, Fmoc-Trp(Boc) release rate solely depended on the PLGA composition that affected polymer degradation rate. The release rate of Fmoc-Trp(Boc) conjugated with fast degrading 50/50 PLGA was more rapid than that conjugated with relatively slow degrading 75/25 PLGA. This study demonstrates that PLGA-drug conjugation approach is a new and novel strategy to control the drug release rate from PLGA microspheres by utilizing the chemical degradation rate of PLGA backbone.
authors.affiliation: Mogam Biotechnology Research Institute, 341 Pojung-ri, Koosung-myun, Yongin, Kyunggido 449-910, South Korea.
authors.forename: J E
authors.initials: JE
authors.lastname: Oh
authors.forename: Y S
authors.initials: YS
authors.lastname: Nam
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: T G
authors.initials: TG
authors.lastname: Park
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009994:Osmolar Concentration; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D018271:Signal Recognition Particle; D012995:Solubility
chemical_list: D001672:Biocompatible Materials; D005079:Excipients; D011108:Polymers; D018271:Signal Recognition Particle; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid