Photochemical crosslinking of hyaluronic acid confined in nanoemulsions: towards nanogels with a controlled structure

Abstract

We present the preparation of nanogels made of hyaluronic acid (HA) with a well-controlled structure. To this end, HA precursors with polymerizable methacrylate groups (HA-MA) were confined within water-in-oil nanoemulsion droplets as nanoreactors and further photopolymerized under UV. Particular attention was paid to the preparation of a stable nanoemulsion template with a homogeneous droplet size. Upon UV irradiation of the emulsion containing HA-MA, crosslinked HA-MA particles with a well-defined size were obtained. Moreover, by varying the photopolymerization conditions, i.e. the number of received photons, we could control the conversion rate of the polymerization, as proved by ¹H-NMR. Nanogels with controlled cross-linking densities were thus obtained. Not only could their crosslinking densities be controlled by the number of incident photons, but also by the degree of methacrylation (DM) of HA-MA derivatives. In addition, the swelling properties of the nanogels depended on external factors, showing their pH and ionic strength responsiveness. We show that these structures were highly biocompatible, stable under storage and enzymatically biodegradable, which opens the route for their application as drug delivery systems. Finally, insulin was loaded in the nanogels and its pH-dependent release was demonstrated. This versatile method of nanogel preparation, which can be applied to every type of hydrophilic precursor, offers a potential synthetic route to design other types of fully biocompatible drug delivery systems.