Analysis and diffusion modelling of a drug delivery system for biomedical applications: Curcumin-loaded PLGA microcarriers, from discrete to continuum domain

Nanomedicine systems offers multiple benefits in treating chronic respiratory and tumoral diseases by site-specific, and target-oriented delivery of precise medicines, employing materials in the nanoscale range. In this context, South Korea has become one of the most active countries. In particular, Yonsei university is one of the most research-intensive institute, with a thriving community of innovative and world-leading researchers. Within this scenario, an heterogenous team in the medical research department of Wonju, composed by nanotechnologists, biologists and engineers, is working on micro-sized polymeric PLGA-based discoidal particles as carriers for the transport and delivery of lung-targeted drugs, in order to improve the therapeutic efficiency and safety of such theranostic systems. The ambitious and innovative work described in this dissertation concerns the simulation of the chemical structure of a drug-loaded PLGA matrix using molecular dynamics simulations with the help of the software Gromacs, in order to obtain a physical diffusion model able to fit the experimental data attained in the laboratory sessions by the research group in Wonju. The nanometric Curcumin-loaded PLGA system was simulated in different conditions, varying the length of PLGA, the density of the polymer and the hydratation level inside the PLGA matrix. These three key parameters have been set in order to create a fractional factorial design of experiment, following the Taguchi method. On the basis of this, a sensitivity analysis of the diffusion phenomenon was performed with the help of the software Minitab, succeeding to obtain a regression model to study. Once it was understood which parameter is the most influential one, further simulations were performed, as to get results of statistical relevance. Last part of the work was dedicated to the simulation of a release model at the microscopic level, in order to fit the results and compare them with the experimental data. It results that the diffusion coefficient calculated in the discrete domain largely underestimates the time needed for the drug to be released. The discrepancies can be traced back to the transition from discrete to continuum scale, in which various phenomena of macroscopic nature are not taken into consideration. Finally, from the fitting of the experimental data obtained in the Wanju laboratory, the effective value of the diffusion coefficient was obtained, also taking into account the phenomenon of degradation by hydrolysis of the PLGA. Contributions of the author: this work was developed in collaboration with Stefano Parlani (Department of Mechanical Engineering, Politecnico di Torino).