Delivering hydrosoluble compounds through the skin: what are the chances?

The epidermis, according to its structure and composition, represents the essential obstacle to the penetration of hydrosoluble drugs, lowering the possibility of being administered by a skin-related route, including epidermal, dermal and transdermal administrations. Even so, drug delivery scientists’ efforts have mainly focused on formulation strategies, such as complex delivery systems, that promote cutaneous and percutaneous absorption of poorly water-soluble drugs. In recent decades, hydrosoluble molecules have become increasingly common in therapy, mainly due to the growing relevance of biological drugs, which would often benefit from a skin-related administration route. Apart from biologicals, other hydrosoluble compounds of interest when referring to the skin are topical antibiotics, anaesthetics, vitamins, or certain cosmeceutical ingredients. Thus, what has been done to increase the chances of delivering hydrosoluble drugs to or through the skin? The current article proposes an up-to-date revision of the complex delivery systems reported in the literature that promote the cutaneous and percutaneous absorption of hydrosoluble compounds, including polymer and lipid micro and nanoparticles, hydrogels, microneedles, 3D-printed and iontophoretic systems published in the last five years. A comprehensive outlook of the permeation mechanisms driving hydrosoluble drugs through the skin is also provided.