期刊
AAPS PHARMSCITECH
卷 20, 期 7, 页码 -出版社
SPRINGER
DOI: 10.1208/s12249-019-1513-x
关键词
huperzine A; microemulsion; nasal administration; dual-responsive in situ gel; microdialysis
资金
- National Natural Science Foundation of China [81973488, 81573615, 81274100]
- National Science and Technology Support Plan [2012BAI26B03]
- Project of Scientific Research Fund of Anhui University of Chinese Medicine [2017zryb002]
- Natural Science Foundation of Anhui Province of China [1608085MH227]
- 2017 Anhui University of Traditional Chinese Medicine Annual Innovation Training Program for College Students [2017171, 2017142]
Huperzine A (hup A), extracted from the Chinese medicinal plant Huperzia serrata, is a reversible and highly selective second-generation acetylcholine esterase (AchE) inhibitor for treating Alzheimer's disease (AD), but it suffers from low bioavailability in the brain. This study aimed to develop a nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of hup A (hup A-M-TPISG). The optimal formulation was obtained by central composite design and response surface methodology. The optimized mucoadhesive formulation, hup A-M-TPISG, was composed of pluronic F127 (20.80%), pluronic F68 (2.8%), and chitosan (0.88%) as the gel matrix, which could gelatinize under physiological conditions (29-34 degrees C, pH 6.5) because of its temperature and pH responsiveness. The optimized hup A-M-TPISG formulation was further evaluated by in vitro release and in vivo pharmacokinetic studies via microdialysis. The in vitro release study showed continuous and steady drug release from hup A-M-TPISG, which was in accordance with the first-order model. Moreover, the pharmacokinetic results revealed that the optimized formulation for nasal administration, with convenient administration and improved patient compliance, could achieve similar brain-targeting properties as intravenous administration. In conclusion, the hup A-M-TPISG for intranasal administration, as an effective and safe vehicle, could enhance the absorption of hup A in vivo and would be a promising noninvasive alternative for partially improving brain-targeting therapy.
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