Transdermal delivery of human growth hormone through RF-microchannels
Transdermal delivery of human growth hormone through RF-microchannels
复制标题
DOI：
10.1007/s11095-005-2498-6
复制
发表时间：
2005-04-01
影响因子：
3.7
通讯作者：
Phillip, M
中科院分区：
文献类型：
--
作者：
Levin, G;Gershonowitz, A;Phillip, M
目的。目的：探讨射频（RF）消融制备的人生长激素（hGH）经皮肤微通道经皮给药的生物利用度和生物活性。亚甲蓝染色后，观察大鼠皮肤和豚鼠皮肤中MCs的形成。在MCs形成后，在大鼠或豚鼠（GP）皮肤上施用不同剂量的干燥形式的生长激素。在贴片应用后15小时，监测两种动物模型中全身生长激素的药代动力学特征。通过测量垂体去皮大鼠的IGF-I水平，验证了经皮递送hGH的生物活性。在放大后的大鼠和豚鼠皮肤上，有序排列的MCs清晰可见。MCs直径均匀，间距相等。MCs在皮肤外层的形成使生长激素的有效递送成为可能，相对于皮下注射（s.c），其生物利用度为75%（大鼠）或33%（普通医生），其血浆谱与s.c注射相似。经皮给药hGH后，观察到全身胰岛素样生长因子-1 （igf -1）水平升高，这表明经皮给药hGH在体内具有生物活性。射频微通道的形成是一个控制良好的过程。这些MCs允许高生物利用度大鼠和gp的生物活性hGH经皮递送。
Purpose. To evaluate the bioavailability and bioactivity of human growth hormone (hGH) delivered transdermally through microchannels (MCs) in the skin created by radio-frequency (RF) ablation.Methods. The creation of MCs was observed in magnified rat and guinea pig skin after staining by methylene blue. Various doses of hGH in a dry form were applied on rat or guinea pig (GP) skin after the formation of MCs. The pharmacokinetic profile of systemic hGH in both animal models was monitored for 15 h post patch application. Bioactivity of the transdermally delivered hGH was verified by measuring IGF-I levels in hypophysectomized rats.Results. The ordered array of MCs was clearly visible in the magnified rat and guinea pig skin. The MCs were very uniform in diameter and of equal separation. Creation of MCs in the outer layers of the skin enabled efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs) relative to subcutaneous (s.c.) injection with plasma profiles resembling that of s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I) were observed after transdermal delivery of hGH to hypophysectomized rats indicative of the bioactivity of the transdermally delivered hGH in vivo.Conclusions. Formation of RF-microchannels is a well-controlled process. These MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high bioavailability.