摘要
目的制备二棕榈酰羟基脯氨酸纳米结构脂质载体(dipalmitoylhydroxyproline nanostructured lipid carriers,DPHP-NLC)及其凝胶,并考察其体外透皮效果。方法采用高压均质法制备DPHP-NLC,以粒径、多分散性指数(polydispersity index,PDI)、Zeta电位和包封率为评价指标,通过单因素试验考察处方工艺对DPHP-NLC制备的影响,运用Box-Behnken Design响应面法进一步筛选最优处方,并将DPHP-NLC制备成凝胶(DPHP-NLC-gel)。采用Franz扩散池法考察DPHP-NLC及DPHP-NLC-gel的体外透皮性能。结果按照最优处方制备的DPHP-NLC分散均匀,平均粒径为(112.0±1.8)nm,PDI为(0.258±0.005),包封率为(97.66±0.56)%。DPHP-NLC和DPHP-NLC-gel在24 h时体外透皮的单位面积累积渗透量(Q24)分别为(102.36±6.10)和(84.22±3.72)μg·cm^(-2),24 h单位面积滞留量分别为(90.60±6.99)和(60.50±3.95)μg·cm^(-2)。DPHP-NLC和DPHP-NLC-gel体外经皮渗透符合Higuchi方程。结论采用高压均质法制备的DPHP-NLC粒径较小,包封率高,提高了DPHP的皮肤透过量及滞留量。
OBJECTIVE To prepare the dipalmitoylhydroxyproline nanostructured lipid carriers(DPHP-NLC)and its gel,and investigate its transdermal effect in vitro.METHODS The DPHP-NLC was prepared by high pressure homogenization,a single factor test was used to investigate the influence of the formulation process on the preparation of DPHP-NLC with the particle size,polydispersity index(PDI),Zeta potential and encapsulation efficiency as evaluation indicators,and the Box-Behnken design effect surface method was used to further screen the optimal formulation.Then,dipalmitoylhydroxyproline nanostructured lipid carriers gels(DPHP-NLC-gel)was prepared,and the in vitro transdermal permeation of DPHP-NLC and DPHP-NLC-gel was evaluated by Franze diffusion cells.RESULTS The DPHP-NLC under the optimal formulation was exhibited good dispersibility,the average particle size was(112.0±1.8)nm,PDI was(0.258±0.005),and the entrapment efficiency was(97.66±0.56)%.The results of in vitro transdermal test showed that the cumulative permeability per unit area in 24 h(Q24)of DPHP-NLC and DPHP-NLC-gel were(102.36±6.10)and(84.22±3.72)μg·cm^(-2)respectively,24 h retention per unit area were(90.60±6.99)and(60.50±3.95)μg·cm^(-2)respectively.Q24and 24 h retention per unit area of the DPHP suspension gel were(60.26±3.12)and(40.58±2.35)μg·cm^(-2)respectively.The in vitro percutaneous penetration of DPHP-NLC and DPHP-NLC-gel accorded with Higuchi equation.CONCLUSION DPHP-NLC prepared by high-pressure homogenization exhibits small particle size and high entrapment efficiency,which improves the skin permeability and retention of DPHP.
作者
余楚钦
汤文静
张碧婷
刘柔佳
周飞容
卫心茹
YU Chu-qin;TANG Wen-jing;ZHANG Bi-ting;LIU Rou-jia;ZHOU Fei-rong;WEI Xin-ru(Guangdong Key Laboratory of New Drug Formulations,Guangdong Local Precision Drug Delivery Preparation Engineering Technology Research Center,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2022年第24期2108-2117,共10页
Chinese Pharmaceutical Journal
基金
广东省药品监督管理局科技创新项目资助(2021TDB40)
广东省林业科技创新项目资助(2022KJCX012)。
关键词
二棕榈酰羟基脯氨酸
纳米结构脂质载体
响应面优化
体外透皮
dipalmitoylhydroxyproline
nanostructured lipid carrier
Box-Behnken design
in vitro transdermal permeation
