A sumatriptan coarse-grained model to explore different environments: interplay with experimental techniques

Abstract

In this work, we developed a coarse-grained model of sumatriptan suitable for extensive molecular dynamics simulations. First, we confirmed the interfacial distribution of this drug in bilayers through cryogenic transmission electron microscopy and small-angle X-ray scattering techniques, as was predicted by our previous atomistic simulations. Based on these simulations, we developed a coarse-grained model for sumatriptan able to reproduce its overall molecular behavior, captured by atomistic simulations and experiments. We then tested the sumatriptan model in a micellar environment along with experimental characterization of sumatriptan-loaded micelles. The simulation results showed good agreement with photon correlation spectroscopy and electrophoretic mobility experiments performed in this work. The particle size of the obtained micelles was comparable with the simulated ones; meanwhile, zeta-potential results suggest adsorption of the drug on the micellar surface. This model is a step forward in the search for a suitable drug-delivery system for sumatriptan.

Study of the Lamellar and Micellar Phases of Pluronic F127: A Molecular Dynamics Approach

“…Broadly, within MFF, four heavy atoms are represented in one site or CG bead. For PL F127, the parameters were taken from previous works [19][20][21]. In particular, detailed information of the used parameters could be found in the supplementary material of reference [19].…”

“…Density profiles are an appropriate measurement for the structural characterization of these systems [19,20,[33][34][35]. For the micellar systems, the radial mass density profiles (rMDPs) were computed by dividing the systems into spherical shells along the radial direction centered at the micellar hydrophobic core and calculating the average density on the respective shells.…”

“…To bridge this gap, coarse-grain (CG) models are useful to accurately simulate these types of system, solving the size and time scale limitations of atomistic simulations [17,18]. Using these models in previous works, we were able to study the self-assembly, stability, and drug-loading capabilities of F127 micelles and their interaction with lipid bilayers [19,20].…”

“…In this work, we studied the molecular, structural, and mechanical properties of F127 micellar and lamellar phases through extensive molecular dynamics simulations from different initial polymer configurations using a CG model previously reported in the literature [19][20][21] for PL F127.…”

Molecular Dynamics Simulations to Study Drug Delivery Systems

“…However, it is argued that in simulations, periodic boundary conditions limit the bilayer undulations that impact the interpretation of the surface tension. In this way, full relaxation of the simulation box (NPT ensemble) is the most used for these kinds of systems [7,[10][11][12][13]].…”