title: In vitro and in vivo characterization of huperzine a loaded microspheres made from end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid).
abstract: The purpose of this work was to develop biodegradable microspheres for long term delivery of a potent acetyl cholinesterase inhibitor, huperzine A (Hup-A), which is of interest in the palliative treatment of Alzheimer's disease. Microspheres were successfully prepared with specifically end-group uncapped poly(d,l-lactide acid) and poly(d,l-lactide-co-glycolide acid) using a simple o/w solvent evaporation method. The morphology, particle size and size distribution, drug loading capacity, drug entrapment efficiency (EE) and in vitro drug release were studied in detail. It was found that the terminal group and the inherent viscosity (IV) of the polymers played key role in the drug encapsulation: higher EE was achieved with end-group uncapped and low IV polymers. In vitro drug release from microspheres made from the selected three kinds of polymers revealed sustained release of Hup-A without significant burst release. Preliminary pharmacokinetic study following subcutaneous injection of Hup-A loaded microspheres illustrated the sustained release of the drug over 6-8 weeks at clinically relevant doses in vivo. The studies demonstrated the feasibility of long term delivery of Hup-A using biodegradable microspheres.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Pingtian
authors.initials: P
authors.lastname: Ding
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Zhenting
authors.initials: Z
authors.lastname: Yuan
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
mesh_terms: D000470:Alkaloids; D000818:Animals; D004339:Drug Compounding; D007279:Injections, Subcutaneous; D019344:Lactic Acid; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014783:Viscosity
chemical_list: D000470:Alkaloids; D018696:Neuroprotective Agents; D011091:Polyesters; D011108:Polymers; D012717:Sesquiterpenes; C050426:huperzine A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)