Injectable Liposome Based Supramolecular Hydrogels for the Programmable Release of Multiple Protein Drugs

Directing and manipulating biological functions is at the heart of next-generation biomedical initiatives. However, the ambitious goal of engineering complex biological networks requires the ability to precisely perturb specific signaling pathways at distinct times and places. Biomaterials that can precisely control drug presentation are therefore critical for advancing next-generation biomedical initiatives such as tissue and immuno-engineering. Using lipid nanotechnology and the principles of supramolecular self-assembly, we set out to develop a novel injectable liposomal nanocomposite hydrogel platform to program the co-release of multiple protein drugs. This report details the mechanical properties and in vivo biocompatibility of these liposomal hydrogels, as well as their ability to simultaneously mediate orthogonal modes of protein release both in vitro and in vivo. Liposomal hydrogels broadly featured shear-thinning and self-healing behaviors enabling facile injectability for local drug delivery applications. By integrating modular lipid nanotechnology into our hydrogel platform, we introduced multiple mechanisms of protein release based on liposome surface chemistry. When injected into immuno-competent mice, liposomal hydrogels were both biodegradable and biocompatible. To fully validate the utility of this system for multi-protein delivery, we demonstrated the synchronized, sustained, and localized release of IgG antibody and IL-12 cytokine in vivo, despite the significant size differences between these two proteins. Overall, liposomal nanocomposite hydrogels are a highly modular platform technology with the potential to precisely coordinate biological cues both in vitro and in vivo.