IN-VITRO MODEL(S) FOR THE PERCUTANEOUS DELIVERY OF ACTIVE TISSUE-REPAIR AGENTS

There is a need to evaluate the permeability of human ulcerated tissue and periulcer tissue in order to assess the possible treatment of suc h a localized pathological lesion with a topical therapy. In vitro per cutaneous absorption studies were undertaken to evaluate an animal mod el that may mimic this clinical situation. Porcine skin from three ana tomical sites, the ear, abdomen, and dorsum; ischaemic skin (porcine a nd guinea pig); porcine wounds; and human skin (including periulcer an d ulcerated tissue) were investigated, utilizing both whole skin and d ermal membranes. Dermal membranes were chosen as representative of ulc erated tissue, as there would be no epidermal barrier present, and the thickness of the dermal membrane was not expected to offer any diffus ional resistance to topically applied active agents. A range of chemic als with differing physicochemical properties was investigated using a Franz type diffusion cell. For all tissues a permeability coefficient (k(p) with units of cm h(-1)) was measured, along with skin thickness and tissue partition coefficient measurements. Under these experiment al conditions and for the range of compounds tested, the results sugge st that porcine skin, whole skin, and dermal membranes should be consi dered as good representative in vitro models for the topical delivery of compounds to human skin and ulcerated tissue, respectively.