In Vitro Percutaneous Absorption Study of Glycols as Penetration Enhancers towards Niacinamide against Skin Models

Abstract

Human skin is the largest organ that covers 16% of the body weight. Normally, skin comprises a multilayer membrane that is known as hypodermis, dermis, and epidermis (Kahraman, et al., 2019). Stratum corneum (SC) is known as the outermost layer of epidermis. It is made up from the binding interaction between corneocytes and lipid interface which includes free fatty acids, cholesterol, and ceramides (Elias & Wakefield, 2010). Stratum corneum also works as the permeability barrier and antimicrobial defenses. In general, the mechanism of barrier function as the permeability is by the regulation of IL-1α, Ca++, pH, liposensors, serine proteases signaling through the PAR2, TRPV1 and 4 as the receptors. Meanwhile, the antimicrobial activity of the skin barrier is regulated by the signaling of 1,25 (OH)2D3, an IL-1α. The signaling pathway of SC as the permeability barrier and antimicrobial defense are occured in lamellar bilayer (Elias, 2008). Moreover, skin is known as the important route for topical and systemic administration (Praça, et al., 2018). Skin naturally is able to regulate the passage of a certain compound to pass through the skin layer, scientifically known as percutaneous absorption. In general, percutaneous absorption is classified into three steps, starting from penetration, permeation, and resorption (Bartosova & Bajga, 2012). Penetration is known as the entry of a particular substance to the SC. Following that, the compound is penetrated from the SC to a deeper layer which has a different function and structure. This process is called permeation. This step is carried out by a diffusion process. The skin permeation is known to be slower than penetration due to the binding of various types of ions (e.g. metal ions, ammonium ions), sulfonium salts, acrylates, etc. SC is mainly used as the rate limiting barrier due to the high resistance to diffusion rate. Meanwhile, resorption is known as the process of uptake of a particular substance into a vascular system. The chemical transport into the skin involves three mechanisms (Bartosova & Bajga, 2012). Transcellular absorption is the process when the particular compound is transferred throughout the keratin-packed corneocytes by a cell membrane partitioning. The mechanism is followed by the intercellular absorption pathway. It occurs when the chemical is moving around the corneocytes which happens in lipid-rich extracellular regions. The end of the second pathway is indicated by the chemicals bypassing the corneocytes and entering the shunts that are provided by the hair follicles, sebaceous glands, and sweat glands. In the percutaneous absorption, a compound that is contacted with skin is generally crossed the diffusional barrier, followed by the uptake by the capillary network that is intended for systemic circulation. However, the compound might undergo evaporation from the surface of the skin. The binding and penetration to SC also possibly occurred as well as the compound is able to be metabolized. Due to the external and internal environment, skin faces some challenges that might decrease its properties. Cosmetics appear as the solution to overcome many skin problems. It is defined as a preparation that is used to clean, beautify, promote attractiveness, alter the body appearance, and also maintain the skin and hair condition (Misui, 1997). Cosmetics are generally classified into skin care, hair care, oral care, and body cosmetics with various pharmacological activities such as anti-aging, anti-wrinkle, whitening agent, cleansing agent, etc. It has been proven that the presence of an active ingredient in cosmetics is expected to exert protective activity, resulting in an improvement of the skin (Kraeling, et al. 2015). However, many of the active ingredients have limited penetration due to many factors, resulting in reduced activity. Therefore, to ensure adequate activity, percutaneous absorption study of the penetration enhancers are important to determine the ability of the penetrant to stimulate the API to penetrate into a deep layer. Percutaneous absorption study is an evaluation of the ability of a certain ingredient to pass through the upper skin membrane. Penetration study is commonly carried out either by in vitro or in vivo test. In vitro penetration test is carried out by applying the cosmetic formulation into multiple types of either human oranimal skin models. It is designated to measure the ability of chemicals to cross the skin membrane into a fluid reservoir. It is appropriately used to predict human dermal penetration study. In vitro method is preferred due to a lower cost, time needed, reproducibility, and less restricted parameters.