Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation
Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation
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DOI：
10.1038/81359
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发表时间：
2000-11-01
期刊：
影响因子：
82.9
通讯作者：
Khavari, PA
中科院分区：
文献类型：
--
作者：
Rothbard, JB;Garlington, S;Khavari, PA
许多全身有效的药物（例如环孢菌素 A）由于对皮肤的渗透性差而局部无效。为了克服这个问题，我们通过 pH 敏感连接体将精氨酸七聚体与环孢菌素 A 缀合，产生 R7-CsA。与无法渗透皮肤的未修饰的环孢菌素 A 相比，局部应用的 R7-CsA 可以有效地转运到小鼠和人类皮肤的细胞中。 R7-CsA 到达真皮 T 淋巴细胞并抑制皮肤炎症。这些数据建立了增强吸收不良的药物穿过组织屏障的递送的一般策略，并为治疗炎症性皮肤病提供了新的局部方法。
Many systemically effective drugs such as cyclosporin A are ineffective topically because of their poor penetration into skin. To surmount this problem, we conjugated a heptamer of arginine to cyclosporin A through a pH-sensitive linker to produce R7-CsA. In contrast to unmodified cyclosporin A,which fails to penetrate skin, topically applied R7-CsA was efficiently transported into cells in mouse and human skin. R7-CsA reached dermal T lymphocytes and inhibited cutaneous inflammation. These data establish a general strategy for enhancing delivery of poorly absorbed drugs across tissue barriers and provide a new topical approach to the treatment of inflammatory skin disorders.