Modeling diffusion in theranostic nanocarriers for biomedical applications: curcumin and PLGA nanoconstructs

In the last few decades enormous efforts have been made in the nanomedicine researching field. Among the several biomedical applications that nanotechnologies could be applied into, the drug delivery systems based on polymer and/or lipid nanoparticles have shown a great potential for the treatment of a large range of respiratory and tumoral diseases as an alternative of the techniques used nowadays. South Korea is one of the most active countries in this field. A team in the Yonsei University medical research department of Wonju, composed by biologists, chemicals and nanotechnologists, is working to improve the efficacy and the safety of micro-sized polymeric particles as treatment carries for lung-target drugs, focusing in particular to study and synthetize PLGA-based discoidal particles. The work explained in this text is aimed to create a model of the chemical structure of the drug-loaded PLGA matrix at nanoscale using the simulation software Gromacs, in parallel with the experimental data obtained from the laboratory session. This collaboration with the research group in Wonju allowed the two authors of this work to investigate in deep the diffusion behavior of the drugs in bulk water and also in the polymeric particles. Two types of drugs are considered in this work. The first is Paclitaxel that is totally analyzed in the thesis made by the other coauthors, the second is the Curcumin that is matter of study in this text in both the configurations: in bulk water and inside the polymeric particle. In the first scenario the drug molecule is simulated with different geometric setups. The Curcumin-loaded PLGA particles were simulated with different configurations based on the dimension of the PLGA, the density of the polymer and the hydration level. The technique of the fractional factorial design was applied to perform a sensitivity analysis on the diffusion phenomenon and to ensure to get results having statistical relevance, and then was possible to reproduce a release profiles of the drugs from the polymer surface, based on the diffusion coefficients obtained from simulations, by a release model created ad hoc. In the end the fitting of the experimental data was performed and also the comparison of the release curves to the trends resulting from the model. In order to demonstrate the goodness and reliability of the developed model and the deviation existing among numerical and experimental values provides an idea of the contribute of degradation phenomenon acting on the PLGA particles when tested in-vivo.