Fujimoto Takahiro, Ito Masayuki, Ito Shinobu, Kanazawa Hideko
a Clinic F , Tokyo , Japan.
b Faculty of Pharmacy , Keio University , Tokyo , Japan.
J Biomater Sci Polym Ed. 2017 May;28(7):679-689. doi: 10.1080/09205063.2017.1296346. Epub 2017 Feb 22.
Liposomes are used for transdermal delivery of drugs and vaccines. Our objective was to develop temperature-responsive (TR) liposomes to achieve temperature-dependent, controlled release of an encapsulated drug, and use fractional laser irradiation to enhance transdermal permeability of these liposomes. TR-liposomes prepared using a thermosensitive polymer derived from poly-N-isopropylacrylamide, N,N-dimethylacrylamide, egg phosphatidylcholine, and dioleoylphosphatidylethanolamine, delivered fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as a model drug. Effect of temperature on liposome size and drug release rate was estimated at two temperatures. Transdermal permeation through hairless mouse skin, with and without CO fractional laser irradiation, and penetration into Yucatan micro-pig skin were investigated using Franz cell and fluorescence microscopy. Dynamic light scattering showed that mean liposome diameter nearly doubled from 190 to 325 nm between 37 and 50 °C. The rate and amount of OVA-FITC released from TR-liposomes were higher at 45 °C that those at 37 °C. Transdermal permeation of OVA-FITC across non-irradiated skin from both TR- and unmodified liposomes was minimal at 37 °C, but increased at 45 °C. Laser irradiation significantly increased transdermal permeation of both liposome groups at both temperatures. Fluorescence microscopy of frozen biopsy specimens showed deeper penetration of FITC from unmodified liposomes compared to that from polymer-modified liposomes. Rhodamine accumulation was not observed with polymer-modified liposomes at either temperature. Temperature-dependent controlled release of an encapsulated drug was achieved using the TR-liposomes. However, TR-liposomes showed lower skin permeability despite higher hydrophobicity. Fractional laser irradiation significantly increased the transdermal permeation. Additional studies are required to control liposome size and optimize transdermal permeation properties.
脂质体用于药物和疫苗的经皮递送。我们的目标是开发温度响应型（TR）脂质体，以实现包封药物的温度依赖性控释，并使用分数激光照射来增强这些脂质体的经皮渗透性。使用源自聚-N-异丙基丙烯酰胺、N,N-二甲基丙烯酰胺、鸡蛋磷脂酰胆碱和二油酰磷脂酰乙醇胺的热敏聚合物制备的TR脂质体，递送异硫氰酸荧光素偶联的卵清蛋白（OVA-FITC）作为模型药物。在两个温度下评估了温度对脂质体大小和药物释放速率的影响。使用Franz扩散池和荧光显微镜研究了有无CO2分数激光照射时，经皮透过无毛小鼠皮肤以及渗透进入尤卡坦微型猪皮肤的情况。动态光散射显示，在37至50°C之间，脂质体平均直径从190nm几乎翻倍至325nm。TR脂质体在45°C时释放OVA-FITC的速率和量高于37°C时。在37°C时，TR脂质体和未修饰脂质体中的OVA-FITC经皮透过未照射皮肤的量极少，但在45°C时增加。在两个温度下，激光照射均显著增加了两个脂质体组的经皮渗透性。冷冻活检标本的荧光显微镜检查显示，与聚合物修饰脂质体相比，未修饰脂质体中的FITC渗透更深。在任一温度下，聚合物修饰脂质体均未观察到罗丹明积累。使用TR脂质体实现了包封药物的温度依赖性控释。然而，尽管TR脂质体疏水性较高，但其皮肤渗透性较低。分数激光照射显著增加了经皮渗透性。需要进一步研究来控制脂质体大小并优化经皮渗透特性。
