title: Naltrexone-loaded poly[La-(Glc-Leu)] polymeric microspheres for the treatment of alcohol dependence: in vitro characterization and in vivo biocompatibility assessment.
abstract: The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-Leu)] copolymer exhibited diminished crystallanity, good biocompatibility and favorable biodegradability to be explored for drug delivery application. Scanning Electron Microscopy study revealed smooth and spherical-shaped NTX-loaded polymeric microspheres with a mean size of 10-90 µm. Influence of various decisive formulation variables such as amount of polymer, stabilizer concentration, homogenization speed, homogenization time, drug loading and organic-to-aqueous phase ratio on particle size, and entrapment efficiency was studied. Differential scanning calorimeter and X-ray diffractometry study confirmed the drug entrapment within polymer matrix into the microsphere environment. In vitro drug release showed the sustained drug release of formulation for the period of 28 d giving biphasic release pattern. Histological examination of NTX-loaded poly[La-(Glc-Leu)] microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that NTX-loaded microspheres were biocompatible. Insignificant increase in the serum creatine phosphokinase level (p < 0.05) as compared with the normal value revealed good muscle compatibility of the poly[La-(Glc-Leu)] microsphere system. Biocompatible nature and sustained drug-release action of poly[La-(Glc-Leu)] microspheres may have potential application in depot therapy.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Section 3 of UGC Act- 1956, Elite Status & Centre of Excellence - Govt. of Maharashtra , TEQIP Phase II Funded, Matunga, Mumbai, Maharashtra , India.
authors.forename: Kunal P
authors.initials: KP
authors.lastname: Pagar
authors.forename: Pradeep R
authors.initials: PR
authors.lastname: Vavia
mesh_terms: D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D007930:Leucine / Q000737:chemistry*; D008863:Microspheres; D009271:Naltrexone / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D011108:Polymers; D012997:Solvents; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009271:Naltrexone; D007930:Leucine