Controlled Release of Small-Molecule Drugs via an Injectable Hydrogel Formed by Cross-Linking of Highly Cross-Linked Nanogels

Maintaining optimal drug concentrations often requires repeated administrations, causing patient inconvenience. Injectable hydrogels that slowly release drugs are promising alternatives but face challenges like high viscosity and large mesh sizes, hindering injection and limiting small-molecule drug delivery.

We propose a novel system utilizing highly cross-linked nanogels (<100 nm) formed from poly (ethylene glycol) diacrylate (PEGDA) monomers. These hyperbranched nanogels maintain low viscosity even at a high concentration, facilitating easy injection. Peroxides generated during polymerization form radicals at body temperature, enabling rapid inter-particle cross-linking with remaining acrylate groups.

Moreover, inter-particle polymerization under concentrated nanogel solutions prevents polymerization-induced phase separation, ensuring that no continuous channels are formed. Cross-linked nanogels with small mesh sizes reduce drug diffusion rates, allowing sustained release.

Rheometer experiments confirmed low viscosity and rapid gelation within 10 minutes at body conditions. In vitro studies using levofloxacin (~1 nm) demonstrated that drug release rates were effectively slowed down.

In conclusion, our nanogel-based injectable hydrogel overcomes existing limitations, enhancing patient convenience and improving small-molecule drug delivery efficiency. This innovative approach holds potential contributions to polymer science and drug delivery fields.