A new PAMPA model proposed on the basis of a synthetic phospholipid membrane

Hui Yu; Qi Wang; Ying Sun; Ming Shen; He Li; Yourong Duan

doi:10.1371/journal.pone.0116502

A new PAMPA model proposed on the basis of a synthetic phospholipid membrane

PLoS One. 2015 Feb 3;10(2):e0116502. doi: 10.1371/journal.pone.0116502. eCollection 2015.

Authors

Hui Yu¹, Qi Wang², Ying Sun², Ming Shen², He Li³, Yourong Duan²

Affiliations

¹ 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.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
³ Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Stability
Humans
Hydrogen-Ion Concentration
Intestinal Absorption
Membranes, Artificial*
Permeability
Phospholipids / chemistry*
Phospholipids / metabolism*

Substances

Membranes, Artificial
Phospholipids

Grants and funding

This research was supported by the Natural Science Foundation of China (No. 81272568, No. 81301973 and No. 81472841) and the Science Foundation for Young Teachers of Wuyi University (No. 2013zk12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.