In Vitro and In Vivo Evaluations of PLGA Microspheres Containing Nalmefene.
Poor patient compliance, untoward reactions and unstable blood drug levels after the bolus administration are impeding the pharmacotherapy for insobriety. A long-acting preparation may address these limitations. The aim of this paper was to further investigate the in vitro characteristics and in vivo performances of nalmefene microspheres. Nalmefene was blended with poly (lactide-co-glycolide) (PLGA) to prepare the target microspheres by an O/O emulsification solvent evaporation method. The prepared microspheres exhibited a controlled release profile of nalmefene in vitro over 4 weeks, which was well fitted with a first-order model. In vitro degradation study showed that the drug release in vitro was dominated by both drug diffusion and polymer degradation mechanisms. Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats. The in vivo pharmacokinetics profile was well correlated with the in vitro drug release. Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats. These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.
Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China.
Xiangyang
X
Xie
Department of Clinical Laboratory, Huangshi Love & Health Hospital of Hubei province, Huangshi, PR China.
Wen
W
Lin
Dalian Merro Pharmaceutical Factory, Dalian, PR China.
Chuanfeng
C
Xing
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing, PR China.
Yanfang
Y
Yang
Department of Pharmacy, The 215th Clinic of 406th Hospital of the Chinese People's Liberation Army, Dalian, PR China.
Qiang
Q
Chi
Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Hui
H
Zhang
Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Ying
Y
Li
Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Zhiping
Z
Li
Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China; Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Yang
Y
Yang
Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Zhenbo
Z
Yang
Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
Mingyuang
M
Li
D000818:Animals; D004337:Drug Carriers; D065546:Drug Liberation; D005260:Female; D006168:Guinea Pigs; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008863:Microspheres; D009271:Naltrexone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009271:Naltrexone; C038981:nalmefene