A Comprehensive Investigation of a Drug Delivery System for Biomedical Purpose: Diffusion of Curcumin in PLGA Microcarriers from Molecular Dynamics to Continuum FEM

Drug delivery systems have been been recently shown as promising technologies for the biomedical research. In this contest, the study of specific carriers that allow drugs to obtain the maximum benefit for the medical treatment from their chemical properties has found in PLGA, Poly-lactic-co-glycolic acid, one of the most adaptable material for diverse delivery needs. Curcumin is an easily available drug with several advantageous medical applications (but insoluble in water). Disparate studies have been done regarding the loading of Curcumin molecules in PLGA microcarriers to allow in-body diffusion for such insoluble drug. The work "Porous discoidal polymeric particles for effective drug delivery minimizing phagocytosis" done by Susmita Aryala and colleagues from the Department of Biomedical Engineering at Yonsei University, has been taken as reference for this research. The aim of this study is to move the first steps in the definition of the effective phenomena that rule the Curcumin diffusion in PLGA carriers. The values for diffusivity and eventually viscosity were obtained in two phases: running molecular dynamics simulations with GROMACS, and post processing the outputs with Matlab codes. Pure Fickian diffusion was considered and Stokes-Einstein's relation was used. The most influential parameter was found thanks to a sensitivity analysis carried out with Taguchi method. Hydration level resulted as the most influential parameter for the simulation, so it was varied to better understand its role in the model. Furthermore, the sensitivity analysis confirmed the robustness of the initial assumptions. With the diffusive coefficient found from MD simulations a continuous FEM simulation was run to fit the experimental data with the simulated ones. It resulted that a pure Fickian diffusion largely underestimates the time period of diffusion, meaning that other elements have a dominant role in the diffusion process. Contribution of the author: this work was developed in collaboration with Alessandro De Giorgi (Department of Nanotechnology, Politecnico di Torino).