Drug-Polymer Interactions in Hydrogel-based Drug-Delivery Systems: An Experimental and Theoretical Study

Abstract

In drug-delivery systems, drug transport is a key step, but the interpretation of the transport mechanism is still controversial. Here, we investigated a promising hydrogel library loaded with the anticonvulsant drug ethosuximide (ESM). The self-diffusion coefficient of ESM was measured using two methods: a direct and advanced measurement with a pulsed field gradient spin-echo (PFGSE) method, using an NMR spectrometer equipped with high-resolution magic angle spinning (HR-MAS) probe, and an indirect one based on fitting in vitro drug-delivery data. Starting from the experimental data a mathematical model without fitted parameters was developed and all the phenomena involved, that is, adsorption and diffusion, were considered. At low drug concentrations, adsorption prevails and consequently the diffusivity in the gels is lower than that in water. At high drug concentrations, where all adsorption sites are saturated, the diffusion in the gels is similar to that in a water solution. This study may pave the way for better device design.

Keywords: HR-MAS NMR spectroscopy; adsorption; drug delivery; hydrogel; transport phenomena.