Centre for Biomedical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi, India.
Drug Dev Ind Pharm. 2010 Aug;36(8):993-1004. doi: 10.3109/03639041003682012.
The main objective of this study was to assess the flux enhancement of insulin transdermally by utilizing a complex of chemical enhancers in combination with modulated iontophoresis.
The experiments were performed on porcine epidermis model under three different circumstances, namely, (a) 1-hour modulated iontophoresis alone; (b) pretreatment with vehicle and chemical enhancer combinations and (c) combination of (a) and (b). The mechanism of action of the enhancers was studied using infra-red spectra by derivative and curve-fitting techniques and Confocal laser scanning microscopy. The efficacy of the optimized combination was tested in vivo in streptozocin-diabetic Wistar rats.
A blend of 1,8 cineole, oleic acid and sodium deoxycholate in propylene glycol : ethanol (7:3) resulted in 45% enhancement, when permeation was performed in combination with iontophoresis as compared to the latter alone. In-depth analysis of infra-red spectra revealed that each of the enhancers acted differentially on lipid-protein domains of the stratum corneum thereby supporting the observed synergism. Movement of fluorescently labeled insulin depicted highlighted follicular regions and paracellular accumulation of the probe after iontophoresis and chemical enhancer treatment respectively. Presence of the fluorescent peptide in these regions 4 hour after treatment with the combination reinforced the results of the permeation studies. Finally the combination of modulated iontophoresis with chemical enhancer blend resulted in lowering of blood glucose for 8 hour in vivo.
The study proved the applicability of modulated iontophoresis with chemical pretreatment in delivering insulin transdermally.
本研究的主要目的是评估利用化学增渗剂复合物与调制离子电渗联合使用对胰岛素经皮渗透的增强作用。
在三种不同情况下（a）单独进行 1 小时调制离子电渗；（b）用载体和化学增强剂组合进行预处理；（c）组合（a）和（b），在猪皮模型上进行实验。使用红外光谱的导数和曲线拟合技术以及共聚焦激光扫描显微镜研究了增强剂的作用机制。在链脲佐菌素诱导的糖尿病 Wistar 大鼠体内，对优化组合的疗效进行了测试。
1,8-桉油醇、油酸和脱氧胆酸钠在丙二醇：乙醇（7:3）中的混合物在与离子电渗联合使用时，与单独使用后者相比，渗透增强了 45%。对红外光谱的深入分析表明，每种增强剂都对角质层的脂质-蛋白质区域产生了不同的作用，从而支持了观察到的协同作用。荧光标记胰岛素的运动描绘了经离子电渗和化学增强剂处理后分别突出的毛囊区域和探针的细胞旁积累。在用该组合处理 4 小时后，这些区域中存在荧光肽，进一步证实了渗透研究的结果。最后，调制离子电渗与化学增强剂混合物的组合在体内将血糖降低了 8 小时。
该研究证明了在经皮传递胰岛素时，调制离子电渗与化学预处理联合应用的适用性。
