Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer
5-Aminolevulinic acid (5ALA) and ester derivates thereof are used as prodrugs in photodynamic therapy (PDT). The behavior of 5ALA and three esters of 5ALA in a DPPC lipid bilayer is investigated. In particular, the methyl ester displays a very different free energy profile, where the highest barrier is located in the region with highest lipid density, while the others have their peak in the middle of the membrane, and also displays a considerably lower permeability coefficient than neutral 5ALA and the ethyl ester. The zwitterion of 5ALA has the highest permeability constant, but a significant free energy minimum in the polar head-group region renders an accumulation in this region.
Edvin Erdtman ab, Daniel J.V.A. dos Santos c, Lennart Löfgren d, Leif A. Eriksson a*
a Department of Natural Sciences, Örebro Life Science Center, Örebro University, Fakultetsgatan 1, 701 82 Örebro, Sweden
b Modelling and Simulation Research Center, Örebro University, Sweden
c i. Med. UL/Institute for Medicine and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon. Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
d Head- and Neck Oncology Center, Örebro University Hospital, 701 85 Örebro, Sweden