Covalently Crosslinked Lipid Nanocapsule-Based Hydrogels Induces the Modern Drug Delivery Efficacy

Saba Niaz ^1*, Guillaume Bastiat Partner ², Patrick Saulnier ²

This study showed a novel covalently crosslinked hydrogel system, enhancing drug delivery via improved mechanical stability and controlled release.

Abstract

Background: The integration of nanotechnology and hydrogel systems offers a promising strategy for localized drug delivery, particularly for hydrophilic and lipophilic drugs with sustained release. Nanoparticle-loaded hydrogels enhance drug pharmacokinetics and biodistribution, opening the door to novel administration routes. However, the potential of these hydrogels has been underutilized due to the reliance on conventional hydrogel architectures. Methods: This study focuses on developing polymer-free lipid nanocapsule (LNC)-based hydrogels using the Michael addition maleimide-thiol reaction to create stable networks. We characterized the viscoelastic properties of these hydrogels by varying LNC concentration, maleimide composition, crosslinker nature, and maleimide/SH molar ratio. Results: Our findings indicate that hydrogel stiffness is significantly influenced by the LNC concentration, maleimide composition, and the nature of the crosslinker. Furthermore, diffusion-based experiments demonstrated that the hydrogel dissolution rate is dependent on the SH PEG crosslinker, while the release behavior of model drugs is influenced by their molecular weight. Conclusion: The study suggests that polymer-free LNC-based hydrogels hold significant potential as drug delivery systems, offering controlled release and reduced toxicity. These findings pave the way for further exploration of novel hydrogel structures in drug administration.

Keywords: Lipid nanocapsules (LNCs), Hydrogels, Covalent crosslinking, Drug delivery systems, Michael addition reaction

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