Archives of Pharmacal Research

  • 제28권9호
  • /
  • Pages.1092-1096
  • /
  • 2005
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

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

  • FU XU-DONG (Department of Pharmacy, Wuhan General hospital of Guangzhou Command) ;
  • GAO YONG-LIANG (Beijing institute of Pharmacology and Toxicology) ;
  • PING QI-LENG (School of Pharmaceutical Sciences, China Pharmaceutical University) ;
  • Ren Tang (Department of Pharmacy, Wuhan General hospital of Guangzhou Command)
  • 발행 : 2005.09.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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.

키워드

참고문헌

  1. Becker, R. and Giacobini, E., Mechanisms of cholinesterase inhibition in senile dementia of the Alzheimer type: Clinical, pharmacological,and therapeutic aspects. Drug Dev. Res., 12, 163-195 (1988) https://doi.org/10.1002/ddr.430120302
  2. Diaz, R. V., Llabre's, M., and E'vora, C., One-month sustained release microspheres of $^{125}I$-bovine calcitonin in vitro-in vivo studies. J. Control. Release, 59, 55-62 (1999). https://doi.org/10.1016/S0168-3659(98)00179-5
  3. Fu, X. D., Ping, Q. N., and Gao, Y. L., Determination of drug content in rat plasma and in injection site after im huperzine A microspheres by high-performance liquid chromatograph method. Chinese. J. Hospital Pharmacy, 24, 465-467 (2004)
  4. Fu, X., Ping, Q., and Gao, Y., Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres. J. Microencapsul., 22, 57-66 (2005) https://doi.org/10.1080/02652040400026509
  5. Li, F. Z. and Sun, M. C., Microcolorimetric assay of cholinesterase activity. Bull. Acad. Mil. Med. Sci., 10, 211-214 (1986)
  6. Okada, H., One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate. Adv. Drug Del. Rev., 28, 43-70 (1997) https://doi.org/10.1016/S0169-409X(97)00050-1
  7. Tang, X. C., Huperzine A (Shuangyiping): A promising drug for Alzheimer's disease. Acta Pharm. Sinica, 17, 481-484 (1996)
  8. Wang, H. and Tang, X. C., Anticholinesterase effects of huperzine A, E2020,and tacrine in rats. Acta Pharm. Sinica, 19, 27-30 (1998)
  9. Woo, B. H., Kostanski, J. W., Gebrekidan, S., Dani, B. A., Thanoo, B. C., and DeLuca, P. P., Preparation characterization and in vivo evaluation of 120-day poly(D,L-lactide) leuprolide microspheres. J. Control. Release, 75, 307-315 (2001) https://doi.org/10.1016/S0168-3659(01)00403-5