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.