Mechanical Properties of Drug Loaded Polymersomes: A Molecular Dynamics Study

DAMIÁN GRILLO; JULIO C. FACELLI; JUAN M. R. ALBANO; MARTA B. FERRARO; ESTEBAN E. MOCSKOS; MONICA PICKHOLZ

Buenos Aires

Congreso; StatPhys 27 Main Conference; 2019

IFIBA, CONICET

This paper presents our investigations of the encapsulation of prilocaine at physiological pH in models of polymeric membranes and polymersomes built with polybutadiene-poly(ethylene oxide) (PBD-PEO).Polymersomes are nanocarriers for targeted drug delivery because they can be used to encapsulate hydrophobic and/or hydrophilic compounds. Their properties depend on the specific characteristics of their polymeric membranes. Prilocaine (PLC) is an anesthetic commonly used in dentistry, which has two different ionization states, neutral (nPLC) and protonated (pPLC), depending on the pH. At physiological pH, there is a partition between both states, pPLC/nPLC, with an estimated equilibrium value of about 1.6 [1].The aim of this work is to evaluate the encapsulation of mixed pPLC/nPLC at physiological pH concentrations on PEO-PBD bilayers and polyermsomes.We used a Coarse Grain (CG) model to study PBD-PEO bilayers and polymersomes by means of Molecular Dynamic (MD) Simulations, employing GROMACS package, and the Martini Force Field (FF) [2].All simulations were carried out using the NPT ensemble. We studied structural and mechanical properties of bilayers and related polymersomes for different pPLC/nPLC concentrations.In order to get insights on the local organization of systems and their mechanical behavior, we analyzed the corresponding mean density profiles, MDPs, and pressure profiles, averaged over the equilibrium trajectories.We also evaluated the elastic properties by characterization of the difference of the adsorbed pPLC molecules on each interface for bilayers and for polymersomes, the spontaneous curvature (H0) and the elastic free energy per unit area (f) for all studied systems.Our results show that the bilayer is suitable to characterize the structure of PLC-loaded membranes, while the polymersome is adequate to study their mechanical properties, providing relevant information to determine the stability of the nanocarriers for different configurations and their mechanical response upon PLC loading.[1] G. Giupponi, M. F. Martini, and M. Pickholz, J. Bio. and T.Eng. 3, 141 (2013); [2] S. J. Marrink, H. J. Risselada, S. Yefimov, D. P. Tieleman, and A. H. de Vries, J.Phys.CHem.B 111, 7812 (2007).