SUMATRIPTAN ENCAPSULATION IN POLOXAMER MICELLES BY MOLECULAR DYNAMICS SIMULATIONS

I. WOOD; M. PICKHOLZ

IGUAZU

Conferencia; I56th International Conference on the Bioscience of lipids; 2015

ICBL

Sumatriptan (SMT) is an antimigraine drug, specially designed as serotonin receptor agonist. SMT has a low partition coefficient. This fact could prevent the drug crossing process through blood-brain barrier, to reach the central nervous system at clinical effective concentrations. In order to improve the sumatriptan efficacy, its incorporation in poloxamer micelles is being proposed. Pluronic® F127 belongs to the family of triblock copolymers of poly(ethylene oxide)?poly(propylene oxide) (PPO)?poly(ethylene oxide) (PEO), generically called poloxamers. Nowadays, these copolymers attract considerable attention as a novel method for the delivery of different drugs, since, above the critical micelle concentration, they aggregate forming micellar structures, besides of being biocompatible. In this work, we have used computer simulations in order to elucidate the encapsulation of SMT in F127 micelles. We carried out classical Molecular Dynamics (MD) simulations using a Coarse Grain (CG) model within the MARTINI force field that can be used to investigate macromolecular phenomena at the microsecond scale [1]. At high concentration, F127 assembles in a micellar structure, having a hydrophobic core and a hydrophilic crown. We developed a coarse grained SMT, based on atomistic simulations. Within this model we have studied the SMT encapsulation into the previous mentioned F127 micelle. Furthermore, it was proposed in the literature that the F127 unimer interaction with membranes could alter their organization, helping the passive diffusion of drugs. In previous work, we have found that F127 adopts a transmembrane conformation, exposing the entire PPO block along the bilayer thickness (since terminals methyl to glycerol groups) and leaving PEO blocks free toward the outside and on both sides of aqueous phase. In this way, we have investigated how the interaction of SMT with membranes is affected by the presence of F127. [1] Marrink, S., e.t al, J. Phys. Chem. B, 2007, 111, 7812.