Efficient Intradermal Delivery of Superoxide Dismutase Using a Combination of Liposomes and Iontophoresis for Protection against UV-Induced Skin Damage
Efficient Intradermal Delivery of Superoxide Dismutase Using a Combination of Liposomes and Iontophoresis for Protection against UV-Induced Skin Damage
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DOI：
10.1248/bpb.35.781
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发表时间：
2012-05-01
影响因子：
2
通讯作者：
Kogure, Kentaro
中科院分区：
文献类型：
--
作者：
Kigasawa, Kaoru;Miyashita, Moeko;Kogure, Kentaro
超氧化物歧化酶（SOD）是一种有效的抗氧化剂，可以防止紫外线引起的皮肤损伤。然而，它的高分子量是有效地通过角质层进入皮肤和发展抗氧化活性的一个重大障碍。最近，我们开发了一种使用脂质体和离子透入相结合的非侵入性大分子经滤泡给药系统，这代表了一种有前途的技术，可以增强带电荷药物的经皮给药（IJP, 403, 2011， Kajimoto等）。在本研究中，我们试图将该系统应用于大鼠皮内给药SOD以防止紫外线引起的皮肤损伤。SOD包封在阳离子脂质体中进行阳极离子电泳。经离子电泳处理后，脂质体在毛囊周围的活皮层中广泛扩散。相比之下，被动扩散不能有效地将脂质体运输到皮肤中。在紫外线照射的皮肤中，包封SOD的脂质体的离子电泳递送导致氧化产物（如丙二醛、己醇基lysine和8-羟基-2-脱氧鸟苷）的产生显著减少。这些发现表明，功能性SOD可以通过离子导入和脂质体系统的结合传递到皮肤中。总之，我们成功地开发了一种高效的皮内SOD递送系统，这将有助于其他大分子的递送。
Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.