Datta Deepanjan, Panchal Dhruvisha Sureshbhai, Venuganti Venkata Vamsi Krishna
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India.
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India.
Int J Pharm. 2021 Jun 1;602:120663. doi: 10.1016/j.ijpharm.2021.120663. Epub 2021 Apr 30.
Topical and transdermal delivery of vancomycin hydrochloride (VH), a broad-spectrum peptide antibiotic, is a challenge because of its high molecular weight (1485.7 Da) and hydrophilicity (log P -3.1). The objective of this study was to investigate the feasibility of delivering VH into and across the skin using permeation enhancement techniques. Skin permeation studies were performed using Franz diffusion cell apparatus in the excised porcine skin model. The influence of co-treatment and pre-treatment of chemical permeation enhancers (oleic acid and palmitic acid) on permeation of VH across intact and tape-stripped skin was evaluated. In addition, continuous anodal iontophoresis was applied to enhance the skin permeation of VH. The mechanism of skin permeation enhancement by palmitic acid was investigated using FTIR spectroscopy, impedance spectroscopy, and thermal analysis techniques. Pharmacokinetic analysis was performed after the topical application of VH formulations in Sprague Dawley rats. Results from permeation studies showed that VH did not passively permeate across the intact skin after 48 h, whereas the cumulative amount of VH permeated across the tape-stripped skin was found to be 854 ± 67 µg/cm. A combination of tape-stripping and chemical enhancers resulted in enhancing the cumulative amount of VH permeated across the skin by 2- and 10-fold with oleic acid and palmitic acid application, respectively. Similarly, 2 and 12 h pre-treatment of tape-stripped skin with palmitic acid enhanced the flux of VH across the skin by 1.7- and 5-fold, respectively. It was found that tape-stripping and the palmitic acid application would provide greater VH permeation compared with 0.31 mA/cm iontophoresis application. Thermal analysis and impedance spectroscopic analysis showed that palmitic acid interacts with epidermal lipids to enhance VH permeation. Pharmacokinetic analysis after topical application showed that the C and mean residence time increased by 3-fold with the application of VH and palmitic acid on tape-stripped skin compared with free VH on intact skin. Taken together, VH can be delivered through the topical route using a combination of chemical enhancer and tape-stripping to treat local and systemic bacterial infections.
盐酸万古霉素（VH）是一种广谱肽类抗生素，由于其分子量高（1485.7道尔顿）和亲水性强（log P -3.1），经皮给药是一项挑战。本研究的目的是研究使用渗透增强技术将VH递送至皮肤内并透过皮肤的可行性。在切除的猪皮肤模型中，使用Franz扩散池装置进行皮肤渗透研究。评估了化学渗透促进剂（油酸和棕榈酸）的联合处理和预处理对VH透过完整皮肤和胶带剥离皮肤的影响。此外，应用连续阳极离子导入法增强VH的皮肤渗透。使用傅里叶变换红外光谱、阻抗光谱和热分析技术研究了棕榈酸增强皮肤渗透的机制。在Sprague Dawley大鼠局部应用VH制剂后进行药代动力学分析。渗透研究结果表明，48小时后VH未被动透过完整皮肤，而透过胶带剥离皮肤的VH累积量为854±67μg/cm²。胶带剥离与化学促进剂联合使用，分别应用油酸和棕榈酸时，可使VH透过皮肤的累积量增加2倍和10倍。同样，用棕榈酸对胶带剥离皮肤进行2小时和12小时预处理，可使VH透过皮肤的通量分别增加1.7倍和5倍。结果发现，与0.31 mA/cm²离子导入法相比，胶带剥离和应用棕榈酸可使VH有更大的渗透量。热分析和阻抗光谱分析表明，棕榈酸与表皮脂质相互作用以增强VH渗透。局部应用后的药代动力学分析表明，与完整皮肤上的游离VH相比，在胶带剥离皮肤上应用VH和棕榈酸后，Cmax和平均驻留时间增加了3倍。综上所述，VH可通过联合使用化学促进剂和胶带剥离的局部给药途径来治疗局部和全身细菌感染。
