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        Preparation and In Vivo Evaluation of Huperzine A-Loaded PLGA Microspheres

        FU XU-DONG,GAO YONG-LIANG,PING QI-LENG,Ren Tang The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.9

        Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an O/w emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with $10\%$ released per day. Thereafter drug release rate became slow gradually and about $90\%$ drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4mg/kg and microspheres were intra­muscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration $(C_{max})$ after i.m. microspheres was only $32\%$ of that after i.m. solution. Drug in plasma could be detectd until day 14 and about $5\%$ of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was $94.7\%$. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

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