title: Controlled release of dutasteride from biodegradable microspheres: in vitro and in vivo studies.
abstract: The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: 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.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The 215th Clinic of 406th Hospital of the Chinese People's Liberation Army, Dalian, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chi
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
authors.forename: ZhiPing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, PR China; Beijing Institute of Pharmacology and Toxicology, Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001378:Azasteroids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068538:Dutasteride; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001378:Azasteroids; D003692:Delayed-Action Preparations; D000068538:Dutasteride