title: A new PAMPA model proposed on the basis of a synthetic phospholipid membrane.
abstract: The purpose of this work was to investigate the synthetic phospholipid dependence of permeability measured by parallel artificial membrane permeability assay (PAMPA) method. Three phospholipids with hydrophobic groups of different lengths and phosphorylcholine as the hydrophilic group were concisely synthesized. Ten model drug molecules were selected because of their distinct human fraction absorbed (%FA) values and various pKa characteristics. In vitro drug permeation experiments were designed to determine the effect of the incubation time (4-20 h), pH gradient (4.6-9.32) and carbon chain length (8, 10, 12) on the drug permeability through the synthetic phospholipid membrane in the PAMPA system. The results showed that intensive and significant synthetic phospholipids dependence of permeability influenced by the length of lipid's hydrophobic carbon chain. The effective permeability constant (Pe) of each drug increased rapidly with time, then decreased slightly after reaching the maximum; the pH gradient changed the drug permeability according to the pH-partition hypothesis for drugs with diverse pKa values; and longer hydrophobic chains in the synthetic phospholipid membrane improved the drug permeability, as observed for all test drugs at almost all incubation time points. This newly proposed PAMPA model considered the synthetic phospholipid membrane and showed good Pe-%FA correlation for the passive transport of drugs, making it a helpful supplementary method for PAMPA systems.
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China; The Engineering Technology Research Center for Functional Textiles in Higher Education of Guangdong Province, College of Textiles and Clothing, Wuyi University, Jiangmen, Guangdong, 529020, China.
authors: Hui
authors: H
authors: Yu
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
authors: Qi
authors: Q
authors: Wang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
authors: Ying
authors: Y
authors: Sun
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
authors: Ming
authors: M
authors: Shen
authors: Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
authors: He
authors: H
authors: Li
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
authors: Yourong
authors: Y
authors: Duan
mesh_terms: D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008567:Membranes, Artificial; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008567:Membranes, Artificial; D010743:Phospholipids
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