Effects of structural features of poloxamers on their interactions with model membranes revealed by coarse grained molecular dynamics simulations

I. WOOD; M.F. MARTINI; M. PICKHOLZ

Foz de Iguazu

Workshop; XLIII Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology (SBBq); 2014

Brazilian Society for Biochemistry and Molecular Biology

Effects of structural features of poloxamers on their interactions with model membranes revealed by coarse grained molecular dynamics simulations Wood, I 1; Martini, MF1,2; and Pickholz, M1,2 1Faculty of Pharmacy and Biochemistry, University of Buenos Aires, 954 Junin St, 6th Floor, CP 1113, Buenos Aires, Argentina, 2CONICET, Buenos Aires, Argentina. The linear triblock copolymers - belonging to the Pluronic® class - are composed by a central hydrophobic poli(propylene oxide) (PPO) block flanked by two identicals hydrophilic poli(ethylene oxide) (PEO) blocks [1]. These amphiphilic, biodegradables, biocompatibles and non immunogenics compounds are mainly used in biomedical and pharmaceutical applications, due to their wide spectrum of properties and effects derived from their varied PEO and PPO composition. The main issue that allows poloxamers applications in these fields is the co-polymer ability to interact with membranes [2]. Coarse grained molecular dynamics (MD) simulations have been performed to investigate the interaction between different poloxamers, at their unimer form, with a fully hydrated 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid bilayer, from different starting localizations. The results have shown dependence of the unimer behaviors on its structural and physico-chemical features. Most of the studied unimers have shown different conformation depending on the starting condition. For instance, when F127 unimer is in contact with the lipid-water interfacial region adopts a compact structure in which the inner hydrophobic domain (PPO) is surrounded by the outer hydrophilic portion (PEO) that remains in contact with water. When is in contact with the bilayer hydrophobic region, F127 displays a trans-membrane conformation, where the PPO block is inserted into the membrane and the PEO chains remain in water on the both sides of the bilayer. The L64 behaves in a different manner compared with F127 and other studied poloxamers. L64 adopts a compact structure at the lipid-water interphase, showing not dependence on starting conditions. Our results provide a picture of the conditions determining poloxamer-bilayer interactions. The interaction degree of certain co-polymers with membranes could justify their use as excipients for drug delivery and as indirect inhibitor of transmembrane efflux proteins, whose over-expression is related with multidrug resistance. Keywords: Poloxamers, POPC, Molecular Dynamics, Coarse grain. References: [1] Pembouong 2011, J. Cont. Rel.; [2] Amado 2011, Curr. Op. Col. Interph. Sci.