Cheruvu Hanumanth Srikanth, Liu Xin, Grice Jeffrey E, Roberts Michael S
Therapeutics Research Centre, The University of Queensland Diamantina Institute, The University of Queensland , Woolloongabba, Australia.
University of South Australia School of Pharmacy and Medical Sciences, The Queen Elizabeth Hospital, Adelaide, Australia.
Expert Opin Drug Discov. 2020 Oct;15(10):1181-1198. doi: 10.1080/17460441.2020.1781085. Epub 2020 Jun 25.
Skin has been used as an administration route for local or systemic action since ancient times. The efficacy and toxicity of any product applied to the skin is determined by the chemical composition and physicochemical properties of the active(s) and excipients, which in turn govern their percutaneous absorption and effects.
This review addresses market trends, skin physiology, solute permeability, formulation properties and effects that are most relevant to a drug discovery scientist designing potentially active solutes for topical application. It also summarizes model strategies, strengths, and limitations associated with the drug delivery design of topical products, with relevant examples.
From a drug discovery perspective, many factors can determine the percutaneous absorption of an active solute. Current models are limited by their dependence on data generated from the permeation of solutes across normal human skin from aqueous solutions. In practice, the choice of formulation, the pertinent skin physiology, and the solute properties, including its clearance, potency, and enhancement, also define dermal delivery. Consequently, there is an emerging trend of using methods to inform effective drug design and development that are based on a combination of QSAR/QSPR with physiologically based pharmacokinetic and pharmacodynamic (PBPKPD) models.
自古以来，皮肤就一直被用作局部或全身作用的给药途径。应用于皮肤的任何产品的功效和毒性取决于活性成分和辅料的化学成分及物理化学性质，而这些性质又决定了它们的经皮吸收和效果。
本综述探讨了与药物发现科学家设计潜在的局部应用活性溶质最为相关的市场趋势、皮肤生理学、溶质渗透性、制剂性质和效果。它还总结了与局部产品给药设计相关的模型策略、优势和局限性，并给出了相关示例。
从药物发现的角度来看，许多因素可以决定活性溶质的经皮吸收。当前的模型受到其对溶质从水溶液透过正常人体皮肤所产生数据的依赖的限制。在实际应用中，制剂的选择、相关的皮肤生理学以及溶质的性质，包括其清除率、效力和增强作用，也决定了皮肤给药。因此，出现了一种新趋势，即使用基于定量构效关系/定量构性关系（QSAR/QSPR）与基于生理学的药代动力学和药效学（PBPKPD）模型相结合的方法来指导有效的药物设计和开发。
