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178 学报 Journal of China Pharmaceutical University 2026, 57(2): 172 − 180 第 57 卷
表 4 各种皮肤药代动力学评价方法的特点
方 法 优 点 不 足
体外 ● 实验结果直观、成本低廉 ● 不适合脂溶性化合物
DC ● 用于药物递送载体设计和优化 ● 人源皮肤组织难以获得
● 渗透膜选择多样(动物或人工膜) ● 无法完全复制体内生理环境
● 能提供快速准确的诊断 ● 设备复杂,定量需校准,可能产生材料干扰
MPS
● 更低的溶剂消耗 ● 皮肤供体来源有限,难以模拟动态生理环境
体内 ● 操作简便、成本低廉 ● 取样周期长
● 防止皮肤瘢痕及活检引起的疼痛
TS ● 主要针对皮肤角质层,无深层皮肤取样
● 易于评估不同角质层深度活性成分的渗透速率和程度 ● 皮肤个体差异会导致检测误差
● 适用于病变的皮肤,用于抗真菌剂、防腐剂、防晒霜等
● 微创、能实时监测不同时间点皮肤组织中游离药物的浓度 ● 不同实验,难以实现一致的皮肤探针植入深度
● 能表征药物在皮肤的吸收和消除
MD ● 主要针对水溶性、游离型药物,脂溶性成分难以检测
● 安全性高,无皮肤组织液的损耗 ● 透析液中药物浓度较低
● 可和HPLC、HPLC/MS等多技术联用
● 不同实验,难以实验一致的皮肤探针植入深度
● 除水溶性小分子药物外,还适用于大分子、脂溶性药物的皮肤取样
OFM ● 样品分析前需要预处理
● 其他同“MD”
● 仅测量总药物量(包括蛋白结合)
● 成本高、操作复杂
● 无创条件下,表征药物在皮肤组织中的渗透和吸收
CRM ● 荧光染料数量有限,成像过程中可能会有荧光干扰
● 可生成高分辨率可视化图像
● 成像速度慢,时间分辨率较低
● 特异性高
MALDI-MSI ● 基质干扰、制样复杂、扫描慢、定量流程复杂
● 高空间分辨率,可同步获取药物与代谢微环境信息
DC:扩散池;MPS:皮肤微生理系统;TS:胶带剥离;MD:微透析;OFM:开放式微灌流;CRM:共聚焦拉曼显微镜;MALDI-MSI:基质辅助激光解吸/电离质
谱成像
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