Synthetic lipopeptides as potential topical therapeutics in wound and skin care: in vitro studies of permeation and skin cells behaviour

Abstract

Wound healing is an extraordinarily complicated process associating with the cell aging, slowing down of cell renewal mechanism and even loss of protective function to environmentally induced oxidative stress. A lack of effective treatment results in the appearance of skin lesions and chronic wounds. A satisfactory answer to skin care and therapy problems seems to be a molecule Gly-His-Lys of natural origin that promotes synthesis of collagen, inhibits the activity of matrix metalloproteinases (MMPs) and reduces the activity of collagenases. Several Gly-His-Lys analogues were obtained to investigate their antimicrobial properties. Three lipophilic analogues with the structure numbering 1b, 2b, 4b, exhibit significant effect against bacteria and were selected for in vitro evaluation of skin cells behaviour. In the present studies, an in vitro model of wound repair, proliferative cell staining, and tracking of living cells were used. Cell proliferation and cell migration, as important actions during the wound repair process, were studied. All the analogues provided an optimal environment for the growth, development and viability of skin cells. Microscopic changes in the morphology of fibroblasts and keratinocytes confirmed the positive effect of all the analogues on their growth and condition. Franz-type diffusion studies and the behaviour of analogues in the in vitro model of permeation were also performed. Permeability and diffusion coefficients were measured using UV-Vis spectrophotometry and RP-HPLC techniques. A substantial increase of permeability parameters for the lipophilic analogues was noticed. The outcomes of these studies suggest that lipophilic analogues possess a high potential as topical therapeutics. In relation with their proved antimicrobial activity, their safety profile and great tolerance for human skin show that they may be applied in both skin care and wound therapies.