Model establishment and parameter optimizing of antineoplastic parallel artificial membrane permeation assay in human lung adenocarcinoma cell line A549

• 1、Department of Biomedicine Engineering, Sichuan University
• 2、Cancer Institute of Shanghai Jiao Tong University, Shanghai
• 3、Department of Biomedicine Engineering, Sichuan University, Chengdu

Abstract：Backgroud and purpose: antineoplastic compounds absorption can depend simultaneously on three interrelated properties: permeability, solubility and pKa. The parallel artificial membrane permeability assay (PAMPA), as a passivepermeability screen, is a possible low-cost alternative to cellular models for the earliest absorption–distribution–metabolism–excretion primary screening of research compounds. Its popularity in the industry has risen rapidly. PAMPA is a useful tool in drug discovery for the prediction of oral absorption, brain penetration and for the development of structure-permeability relationships. This study was to examine state-of-the-art PAMPA methods and establish a tumor cell membrane model, and predict the cell antineoplastic absorption. Methods: Based on analyzing the standard gastrointestinal permeability model, the method of predicting antineoplastic permeability was advanced by experimental condition optimization, and the possible permeability models of tumor cell membrane was given. Results: Experimental PAMPA data generated for 16 commercial drugs was compared with cell absorption value, the result showed that the optimized correlation degree was 0.77. Conclusions: The parallel artificial membrane permeation assay (PAMPA) permits the fast determination of artificial membrane permeation properties of drugs, which will help to develop new anticarcinogen with better bioavailibility

Keywords： parallel artificial membrane permeability assay (PAMPA) tumor cell membrane permeability drug screening orthogonal test