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Negatively charged skin surface proteins refer to the collective group of anionic proteins located within the stratum corneum, the outermost layer of the epidermis. These proteins, which include keratins, filaggrin, and various cornified envelope proteins (such as involucrin and loricrin), possess a net negative charge at the physiological pH of the skin surface, which typically ranges from 4.5 to 5.5. This anionic property is a fundamental component of the skin's "acid mantle," serving as a critical barrier against environmental pathogens and helping to maintain skin hydration through the retention of natural moisturizing factors. In pharmacology and dermatology, these proteins are the primary target for cationic (positively charged) topical agents, such as the antiseptic chlorhexidine and quaternary ammonium compounds like benzalkonium chloride. The electrostatic attraction between these positively charged drugs and the negatively charged skin proteins leads to a phenomenon known as "substantivity," where the drug remains bound to the skin for extended periods, providing a persistent residual antimicrobial effect. Alterations in the composition, expression, or charge density of these proteins are frequently observed in dermatological conditions such as atopic dermatitis and ichthyosis, where the skin's barrier function is compromised and susceptibility to infection is increased.
Electrostatic binding to anionic skin surface sites resulting in substantivity and residual antimicrobial activity.
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