Kai T, Isami T, Kurosaki Y, Nakayama T, Kimura T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biol Pharm Bull. 1993 Mar;16(3):284-7. doi: 10.1248/bpb.16.284.
Model lipid mixtures composed of ceramide (40%), cholesterol (25%), palmitic acid (25%) and cholesterol 3-sulfate (10%) were used as the model for intercellular lipids of stratum corneum (SC) to evaluate a barrier function of SC for drug permeation. Six beta-blockers, propranolol, metoprolol, timolol, pindolol, nadolol and atenolol, were used as the model permeants. The maximum flux values (observed flux/thermodynamic activity, Jmax) of drugs through the membrane coated with the model lipid mixtures and two keratinized membranes, rat skin and hamster cheek pouch, were determined in vitro using a Franz-type diffusion cell. Further, drug partition coefficients to the multilamellar liposomes prepared by the model lipid mixtures were determined. The Jmax values obtained in the model lipid-coated membrane, in the intact rat skin and in the intact hamster cheek pouch mucosa, bore a linear relationship to each other. These results suggest that the model lipid-coated membrane is a useful tool for the prediction of the drug permeability through the keratinized membrane in the in vitro system. The Jmax values also correlated with drug partition to the model lipid liposomes, suggesting the validity of the use of the model lipid mixtures as the substitutes for the intercellular lipids of the stratum corneum.
由神经酰胺（40%）、胆固醇（25%）、棕榈酸（25%）和胆固醇3 - 硫酸盐（10%）组成的模型脂质混合物被用作角质层（SC）细胞间脂质的模型，以评估SC对药物渗透的屏障功能。六种β受体阻滞剂，普萘洛尔、美托洛尔、噻吗洛尔、吲哚洛尔、纳多洛尔和阿替洛尔，被用作模型渗透剂。使用Franz型扩散池在体外测定药物通过涂有模型脂质混合物的膜以及两种角质化膜（大鼠皮肤和仓鼠颊囊）的最大通量值（观察通量/热力学活性，Jmax）。此外，还测定了药物对由模型脂质混合物制备的多层脂质体的分配系数。在涂有模型脂质的膜、完整的大鼠皮肤和完整的仓鼠颊囊黏膜中获得的Jmax值彼此呈线性关系。这些结果表明，涂有模型脂质的膜是体外系统中预测药物通过角质化膜渗透性的有用工具。Jmax值还与药物在模型脂质脂质体中的分配相关，表明使用模型脂质混合物作为角质层细胞间脂质替代物的有效性。
