Walker M, Hulme T A, Rippon M G, Walmsley R S, Gunnigle S, Lewin M, Winsey S
Advanced Tissue Repair R & D, ConvaTec Wound Healing Research Institute, Deeside, Flintshire, UK.
J Pharm Sci. 1997 Dec;86(12):1379-84. doi: 10.1021/js970159i.
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.
为了评估通过局部治疗来处理这种局限性病理病变的可能性，有必要评估人类溃疡组织和溃疡周围组织的渗透性。开展了体外经皮吸收研究，以评估一种可能模拟这种临床情况的动物模型。研究了来自三个解剖部位（耳朵、腹部和背部）的猪皮肤、缺血皮肤（猪和豚鼠）、猪伤口以及人类皮肤（包括溃疡周围组织和溃疡组织），使用了全皮和真皮膜。选择真皮膜作为溃疡组织的代表，因为不存在表皮屏障，并且预计真皮膜的厚度不会对局部应用的活性剂产生任何扩散阻力。使用Franz型扩散池研究了一系列具有不同物理化学性质的化学物质。对于所有组织，测量了渗透系数（kp，单位为cm h-1），以及皮肤厚度和组织分配系数。在这些实验条件下以及对于所测试的化合物范围，结果表明猪皮肤、全皮和真皮膜应分别被视为将化合物局部递送至人类皮肤和溃疡组织的良好代表性体外模型。
