Lee Woan-Ruoh, Pan Tai-Long, Wang Pei-Wen, Zhuo Rou-Zi, Huang Chun-Ming, Fang Jia-You
Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan.
J Control Release. 2008 Jun 24;128(3):200-8. doi: 10.1016/j.jconrel.2008.03.003. Epub 2008 Mar 10.
Transdermal delivery of peptides and the related vaccines is attractive for treatment and prevention of diseases. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The objective of this study was to enhance and control skin permeation of peptides and related vaccines using an erbium:yttrium-aluminum-garnet (Er:YAG) laser. The amount of peptide transported through nude mouse skin was measured using a Franz diffusion apparatus. The SC layer was partly ablated by an Er:YAG laser, resulting in a greater enhancement effect on peptide delivery. A thinned and discontinuous SC layer was observed after laser exposure. The flux of peptides across skin treated with a laser at various fluences was 3-140-fold higher than that across intact skin. The molecular size, lipophilicity, and sequence of the peptides were found to play important roles in modulating the enhancement of activity. The result of confocal laser scanning microscopy (CLSM) indicated a significant increase in the skin deposition of peptides into laser-treated skin. In an in vivo study, mouse skin was treated with the laser followed by skin vaccination with a lysozyme antigen. It was demonstrated for the first time that laser treatment with no adjuvant or penetration enhancer significantly enhanced the production of antibodies in the serum by 3-fold. To reveal the mechanisms underlying these changes, a proteomic technique combined with mass spectrometry was used. This is, to our knowledge, the first report of a laser being used to immunize intact animals.
肽类及相关疫苗的经皮递送对于疾病的治疗和预防具有吸引力。然而，这种递送方法受到角质层（SC）低渗透性的限制。本研究的目的是使用铒：钇铝石榴石（Er：YAG）激光增强并控制肽类及相关疫苗的皮肤渗透。使用Franz扩散装置测量通过裸鼠皮肤转运的肽量。Er：YAG激光部分消融了SC层，从而对肽递送产生了更大的增强作用。激光照射后观察到SC层变薄且不连续。在不同能量密度下用激光处理的皮肤中肽的通量比完整皮肤高3 - 140倍。发现肽的分子大小、亲脂性和序列在调节活性增强方面起重要作用。共聚焦激光扫描显微镜（CLSM）的结果表明，肽在激光处理皮肤中的皮肤沉积显著增加。在一项体内研究中，先用激光处理小鼠皮肤，然后用溶菌酶抗原进行皮肤疫苗接种。首次证明，在不使用佐剂或渗透促进剂的情况下，激光处理可使血清中抗体的产生显著增强3倍。为了揭示这些变化背后的机制，使用了蛋白质组学技术结合质谱法。据我们所知，这是首次报道使用激光对完整动物进行免疫。
