The stability of insulin in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol.
Insulin-loaded microparticles were produced from blends of poly(ethylene glycol) (PEG) with poly (L-lactide) (PLA) homopolymer and poly (DL-lactide co-glycolide) copolymers (PLG) using a water-in-oil solvent extraction method. The dispersed phase was composed of PLG/PEG or PLA/PEG dissolved in dichloromethane, and the continuous phase was methanol containing 10% PVP. Characteristics, including particle size distribution, insulin loading capacity and efficiencies, in vitro release, degradation and stability, were investigated. The stability of insulin associated with microparticles prepared using PEG and 50:50 PLG and PLA was analysed by HPSEC and quantified by peak area following incubation in PBS at 37 degrees C for up to 1 month. Insulin was successfully entrapped in the PLG/PEG and PLA/PEG microparticles with trapping efficiencies up to 56 and 48%, loading levels 17.8 and 10.6% w/w, and particle sizes 8 and 3 microm, respectively. The insulin-loaded PLG/PEG and PLA/PEG microparticles were capable of controlling the release of insulin over 28 days with in vitro delivery rates of 0.94 and 0.65 microg insulin/mg particles/day in the first 4 days and a steady release with rate of 0.4 and 0.43 microg insulin/mg particles/day over the following 4 weeks, respectively. Extensive degradation of the PLG/PEG microparticles also occurred over 4 weeks, whereas the use of PLA/PEG blends resulted in a stable microparticle morphology and much reduced fragmentation and aggregation of the associated insulin.
Yeh
M K
MK
Department of Clinical Pharmacy, Tri-service General Hospital, Taipei, Taiwan. mkyeh@ndmcl.ndmctsgh.edu.tw
D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D007328:Insulin; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)