4.5 Article

In vitro skin model for the evaluation of burn healing drug delivery systems

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ELSEVIER
DOI: 10.1016/j.jddst.2021.102330

Keywords

Skin model; Transepidermial water loss; Drug penetration; Tape-stripping; Wound healing

Funding

  1. FAP-DF (Fundacao de Apoio a Pesquisa do Distrito Federal, Brazil) [00193-00001252/2019-18]
  2. CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil) [406636/2016-8]
  3. CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil)

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This study developed an in vitro burnt skin model using a hot plate on porcine skin to simulate first and second-degree burn conditions and evaluated drug permeation. The results indicated that drug penetration significantly increased in situations of second-degree burns, regardless of drug lipophilicities.
This study aims to develop an in vitro burnt skin model to be used in permeation experiments during the research and development of topical formulations for wound healing. For this, a hot plate at 85 +/- 1 degrees C was placed in direct contact with porcine skin for 4, 7, or 10 s. Injury level was evaluated according to skin transepidermal water loss (TEWL) and histological profile, and compared to tape-stripped skin (10, 20, or 30 tapes), a well-known tech-nique for damaging the skin barrier. Also, the permeation of three model drugs with different lipophilicities (catechin, Log P = 1.8; clindamycin phosphate, Log P = 0.9; and ketoconazole, Log P = 4.3) in all injured samples was assessed. TEWL evaluations showed that the skin burnt for only 4 s already reached a critical dehydration condition (30.9 +/- 1.0 g/h/m(2)), while the tape-stripped skin only reached such a critical TEWL state after the removal of 30 tapes (38.5 +/- 3.6 g/h/m(2)). Histological evaluation showed the tape-stripping procedure causes damage equivalent to a first-degree burn. In contrast, progressive skin burn can reproducibly simulate first and superficial or deep second-degree burn conditions, just by adjusting the hot plate's contact time. Noticeably, there were significant increases in drug permeation to the epidermis in situations of second-degree burns regardless of drug lipophilicities. In conclusion, a reliable, inexpensive, and easy-to-handle in vitro burnt skin model can be obtained by applying a hot plate on porcine skin. Such a model might be extremely useful to study drug penetration through burnt skin.

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