常绿钩吻碱壳聚糖微乳温敏凝胶的制备及质量评价  

Preparation and quality evaluation of sempervir in echitosan thermosensitive microemulsion-based hydrogel

作　　者：宋煜[1] 蒋文文 林欣欣 陈惠娴 许文[1] 吴水生[1,2] SONG Yu;JIANG Wenwen;LIN Xinxin;CHEN Huixian;XU Wen;WU Shuisheng(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fujian Fuzhou 350122,China;Fujian Provincial Development Base of Traditional Chinese Medicine Industry Technology,Fujian Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]福建省中药产业技术开发基地,福建福州350122

出　　处：《中国医院药学杂志》2024年第17期2015-2020,共6页Chinese Journal of Hospital Pharmacy

基　　金：福建省科技厅引导性项目(编号:2020Y0051);福建省技术创新重点攻关及产业化项目(编号:2023XQ006)。

摘　　要：目的:优化常绿钩吻碱壳聚糖微乳温敏凝胶(SPV-CTMH)处方并对其进行质量评价。方法:以胶凝温度作为考察指标,结合单因素实验与星点设计-效应面法对常绿钩吻碱微乳温敏凝胶(SPV-TMH)处方进行优化;采用Franz扩散池法考察处方中加入不同浓度的壳聚糖后SPV-CTMH的黏膜渗透和细胞毒性情况,以选择合适的壳聚糖浓度,并对优化后的SPVCTMH的外观、pH值、黏度和黏膜渗透等状况进行考察。结果:SPV-TMH最优处方选择泊洛沙姆188含量为4.21%(W/V),泊洛沙姆407含量为16.92%(W/V);添加0.2%以上浓度的壳聚糖后可明显改善药物的黏膜渗透情况,并能显著提高体外抑制U251细胞增殖的能力,最终选择加入0.2%(W/V)浓度的壳聚糖;所制SPV-CTMH的含药量为(1.099±0.001)mg·mL^(-1),pH值为6.03±0.05,Zeta电位为(24.09±1.37)mV,粒径为(32.7±1.9)nm,胶凝前流动顺畅,胶凝后黏度显著增加,并显著改善了常绿钩吻碱的黏膜渗透。结论:所制备得到的SPV-CMTH质量优良,应用于鼻腔给药有望提升疗效。OBJECTIVE To optimize the formulation and evaluate the quality of sempervirine chitosan thermosensitive microemulsion-based hydrogel(SPV-CTMH).METHODS The formulation of SPV-TMH was optimized by combining single-factor experiments with central composite design-response surface method using gelling temperature as an index.Franz diffusion cell method was utilized for examining mucosal permeation profile and cytotoxicity of SPV-CTMH after adding chitosan at different concentrations for determining an appropriate concentration.Furthermore,appearance,pH,viscosity and mucosal permeation properties of optimized SPV-CTMH were examined.RESULTS The optimal formulation of SPV-TMH contained 4.21%(W/V)for poloxamer 188 and 16.92%(W/V)for poloxamer 407.With the addition of not less than 0.2% chitosan,mucosal permeation of the drug improved markedly and there was a greater inhibition of U251 cell proliferation.Therefore 0.2%chitosan was selected as an optimal formulation.The prepared SPV-CTMH contained(1.099±0.001)mg·mL^(-1) of drug with a pH of(6.03±0.05),a zeta potential of(24.09±1.37)mV and a particle size of(32.7±1.9)nm.SPV-CTMH demonstrated a smooth flow before gelation and marked increases in both viscosity after gelation and mucous membrane permeation of sempervirine.CONCLUSION The prepared SPV-CTMH has desirable characteristics and its application for nasal drug delivery is expected to enhance the therapeutic efficacy.

关 键 词：常绿钩吻碱 星点设计-效应面法 壳聚糖 微乳 温敏凝胶 

分 类 号：R932[医药卫生—生药学]