Controlled release of huperzine A from biodegradable microspheres: In vitro and in vivo studies.
The objective of the present work was to further study the in vitro characteristics, in vivo pharmacokinetics and pharmacodynamics of huperzine A (HupA) loaded biodegradable microspheres designed for sustained release of HupA over several weeks. A conventional o/w emulsion-solvent evaporation method was used to incorporate HupA, which is of interest in the palliative treatment of Alzheimer's disease (AD), into end-group uncapped poly(D,L-lactide-co-glycolide) (PLG-H). A prolonged in vitro drug release profile was observed, with a complete release of the incorporated drug within 5-6 weeks. The in vivo pharmacokinetics study of HupA loaded microspheres showed sustained plasma HupA concentration-time profile after subcutaneous injection into rats. The pharmacodynamics evaluated by determination of the activity of acetylcholinesterase in the rat cortex also showed a prolonged pharmacological response. Both the in vitro release and in vivo pharmacological responses correlated well with the in vivo pharmacokinetics profile. The results suggest the potential use of HupA-loaded biodegradable microspheres for treatment of AD over long periods.
Gao
Ping
P
Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 10016, China.
Xu
Hui
H
Ding
Pingtian
P
Gao
Qizhen
Q
Sun
Jingyi
J
Chen
Dawei
D
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004355:Drug Stability; D019344:Lactic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D011108:Polymers; D012717:Sesquiterpenes; C050426:huperzine A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000110:Acetylcholinesterase