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 such a localized pathological lesion with a topical therapy. In vitro percutaneous absorption studies were undertaken to evaluate an animal model that may mimic this clinical situation. Porcine skin from three anatomical sites, the ear, abdomen, and dorsum; ischaemic skin (porcine and guinea pig); porcine wounds; and human skin (including periulcer and ulcerated tissue) were investigated, utilizing both whole skin and dermal membranes. Dermal membranes were chosen as representative of ulcerated tissue, as there would be no epidermal barrier present, and the thickness of the dermal membrane was not expected to offer any diffusional resistance to topically applied active agents. A range of chemicals with differing physicochemical properties was investigated using a Franz type diffusion cell. For all tissues a permeability coefficient (kp with units of cm h-1) was measured, along with skin thickness and tissue partition coefficient measurements. Under these experimental conditions and for the range of compounds tested, the results suggest that porcine skin, whole skin, and dermal membranes should be considered as good representative in vitro models for the topical delivery of compounds to human skin and ulcerated tissue, respectively.
Walker
M
M
Advanced Tissue Repair R & D, ConvaTec Wound Healing Research Institute, Deeside, Flintshire, UK.
Hulme
T A
TA
Rippon
M G
MG
Walmsley
R S
RS
Gunnigle
S
S
Lewin
M
M
Winsey
S
S
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D007871:Leg Ulcer / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D010080:Oxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D010539:Permeability; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012867:Skin / Q000098:blood supply / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption; D013552:Swine; D014947:Wounds and Injuries / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D017482:Receptors, Thromboxane; D003907:Dexamethasone; C078904:ifetroban; D001241:Aspirin