Lin Hongxia, Yoo Jin-Wook, Roh Hwan-Jung, Lee Min-Ki, Chung Suk-Jae, Shim Chang-Koo, Kim Dae-Duk
College of Pharmacy, Pusan National University, Pusan 609-735, South Korea.
Eur J Pharm Sci. 2005 Oct;26(2):203-10. doi: 10.1016/j.ejps.2005.06.003.
The purpose of this study was to investigate the nasal absorption characteristics of a series of anti-allergic drugs across the human nasal epithelial cell monolayer, which was passage cultured by the liquid-covered culture (LCC) method on Transwell. Characterization of this cell culture model was achieved by bioelectric measurements and morphological studies. The passages 2--4 of cell monolayers exhibited the TEER value of 1731+/-635 Omega cm(2) after 2 days of seeding and maintained high TEER value for 4--6 days. Morphological study by TEM and SEM showed the existence of the tight junctions, and the cuboidal shaped epithelial cells monolayer. A series of anti-allergic drugs, albuterol hemisulfate, albuterol, fexofenadine HCl, dexamethasone, triamcinolon acetonide, and budesonide were selected as model compounds for transport studies. All the drugs were assayed using reversed-phase HPLC under isocratic conditions. Results indicated that within the logP (apparent 1-octanol/water partition coefficient) range from --1.58 (albuterol) to 3.21 (budesonide), there existed 100-fold difference in the apparent permeability coefficients (P(app)). A log-linear relationship was shown between the drug logP and the P(app) across passaged human nasal epithelial monolayers. The amount of fexofenadine HCl and dexamethasone across passaged human nasal cell monolayers was concentration-dependent in the direction of apical to basolateral. The direction dependent transport studies were investigated among all these drugs and no significant difference in the two directions was observed. In conclusion, this LCC passaged human nasal epithelial culture model may be a useful in vitro model for studying the passive transport processes in nasal drug delivery.
本研究的目的是研究一系列抗过敏药物在人鼻上皮细胞单层中的鼻吸收特性，该细胞单层是通过在Transwell上采用液封培养（LCC）方法传代培养的。通过生物电测量和形态学研究实现了对该细胞培养模型的表征。细胞单层传代2至4代在接种2天后表现出1731±635Ω·cm²的跨上皮电阻（TEER）值，并在4至6天内保持较高的TEER值。通过透射电子显微镜（TEM）和扫描电子显微镜（SEM）进行的形态学研究显示存在紧密连接以及立方体形上皮细胞单层。选择一系列抗过敏药物，硫酸沙丁胺醇、沙丁胺醇、盐酸非索非那定、地塞米松、曲安奈德和布地奈德作为转运研究的模型化合物。所有药物均在等度条件下使用反相高效液相色谱法进行测定。结果表明，在logP（表观正辛醇/水分配系数）范围从-1.58（沙丁胺醇）至3.21（布地奈德）内，表观渗透系数（P(app)）存在100倍的差异。在传代的人鼻上皮单层中，药物logP与P(app)之间呈现对数线性关系。盐酸非索非那定和地塞米松跨传代人鼻细胞单层的量在从顶侧向基底侧的方向上呈浓度依赖性。对所有这些药物进行了方向依赖性转运研究，未观察到两个方向上有显著差异。总之，这种LCC传代的人鼻上皮培养模型可能是一种用于研究鼻药物递送中被动转运过程的有用体外模型。
