目的 探究金属阵列微针对皮肤的预处理方式对盐酸雷莫司琼贴片经皮给药促透作用的影响。方法 自制盐酸雷莫司琼贴片与金属阵列微针(以下简称微针)联合应用,通过析因实验设计,考察微针类型、长度、预处理皮肤的作用力和作用时间4个主要因素对药物经离体豚鼠皮肤渗透的促进作用,并进行了影响因素的主效应和交互效应分析。结果 微针长度对微针促透效果的影响最明显,微针长度由200 μm提高到300 μm,稳态渗透速率以及48 h累积渗透量增加明显。微针处理皮肤的作用力与微针长度对药物经皮促透效果有交互影响,当微针作用时间以及微针类型一定时,微针长度200 μm,作用力在3~5 N内变化未对微针的经皮促透效果产生明显影响,微针长度为300 μm时,作用力增加对药物促透效果明显。结论 提示微针对皮肤的预处理方式对盐酸雷莫司琼经皮渗透效果有重要影响,预处理方式间存在交互效应,本实验为微针辅助经皮给药中的微针预处理方式选择提供参考。

OBJECTIVE To evaluate the effects of different pretreatment ways on microneedle onits penetration enhancing effect for ramosetron hydrochloride paches in microneedle-assisted transdermal drug delivery. METHODS Skin penetration experiments were carried out using excised guinea pig skin. Microneedle pretreatment ways including needle type, needle length, needle acting force and acting time were taken as the influencing factors. The main effects and interaction effects of influencing factors in skin penetration enhancement were analyzed. RESULTS Microneedle length had the most significant impact on drug skin penetration. When the length changed from 200 μm to 300 μm, the steady-state permeation rate and the cumulative permeation amount within 48 h displayed marked increase. Additionally, there was interaction between the penetration enhancing effects of the microneedle length and acting force. When the acting time and needle type were fixed and the microneedle length was 200 μm, no significantly different impacts occurred if the acting force varied between 3 and 5 N. However, if the microneedle length was 300 μm, the penetration enhancing effects became more significant when increasing acting force from 3 to 5 N. CONCLUSION This studies suggeste that microneedle pretreatment ways may result in different effects on penetration of drugs through skin, and there may exist interaction effect between different microneedle pretreatment ways.This study provides a reference for the selection of microneedle pretreatment in microneedle-assisted transdermal drug delivery.