63
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I
9-POS
Board 9
Phospholipase A
2
Action on Lipid-based Drug Delivery Systems
Ahmad Arouri
, Anders H. Hansen, Ole G. Mouritsen.
University of Southern Denmark, Odense, Denmark.
Lipid-based delivery systems have intensively been used to enhance the physico-chemical
properties and to modify the pharmacokinetic profiles of drugs, with many successful attempts.
In anticancer drug delivery, the small size of the carriers can promote their accumulation is leaky
cancer tissues. However, the need to construct liposomes that are stable during storage and in the
blood stream is very often associated with a modest and slow release of the payload at the target.
This calls for “smarter” strategies to actively unload the drug precisely at the target.
Our platform is based on benefiting from secretory phospholipase A
2
(sPLA
2
) overexpressed in
several cancer types to actively release anticancer drugs. The generated hydrolysis products, i.e.
fatty acids and lysolipids, can also serve as cytotoxic agents and permeability enhancers, both at
the carrier and target cell membranes. This approach opened new venues for designing lipase-
sensitive liposome-forming lipid prodrugs, where the fatty acid at position
sn
-2 has been
replaced by anticancer drugs. The enzymatic action of sPLA
2
on lipid carriers is strongly
influenced by the lipid (substrate) chemical structure, lipid membrane composition, payload, and
lipid/enzyme ratio.
References:
T. L. Andresen, S. S. Jensen, and K. Jørgensen, Prog. Lipid Res. 44, 197–224
(2005); A. Arouri and O. G. Mouritsen, J. Liposome Res. 21, 296-305 (2011); A. Arouri and O.
G. Mouritsen, Eur. J. Pharm. Sci. 45, 408-420 (2012); A. Arouri and O. G. Mouritsen, Prog.
Lipid Res. 52, 130-140 (2013); A. Arouri, A. H. Hansen, T. E. Rasmussen, and O. G. Mouritsen,
Curr. Opin. Colloid Interface Sci. 18, 419-431 (2013).
