Nail micro-environment acidification

Nail micro-environment acidification refers to the pH-dependent phenomena occurring within and around the nail plate structure. The nail plate, composed primarily of keratin proteins with an isoelectric point around pH 4.7-5.0, exhibits pH-dependent charge characteristics that significantly influence drug permeation and barrier properties. At pH values above 5, the nail plate becomes negatively charged, while below pH 5 it becomes positively charged. This charge state affects the transport of ionizable drugs through the Donnan equilibrium effect, where the nail plate can either enhance or hinder drug permeation based on the charge of the drug molecule and the pH of the formulation. The acidification or pH modulation of the nail micro-environment is a critical consideration in transungual drug delivery, particularly for treating fungal infections, as it affects drug partitioning, ionization state, and overall permeability through this formidable barrier composed of approximately 196 cell layers with extensive disulfide cross-linking and limited hydration.

Other names

Nail plate pH modulationTransungual pH environmentNail keratin acidification

As a physiological process, pH modulation affects drug ionization state and permeability, influences Donnan equilibrium effects on charged drug transport, alters keratin protein charge (negatively charged at pH > 5, positively charged at pH < 5), and thereby enhances or reduces transungual drug penetration based on drug pKa and formulation pH.