Increase Nebulization Stability of Lipid Nanoparticles by Integrating a DNA Supramolecular Hydrogel

Nebulized lipid nanoparticles (LNPs) have been considered as potential therapies for genetic disease as well as infectious disease. However, the sensitivity of LNPs to high shear stress during the nebulization process results in loss of the integrity of the nanostructure and the capability of delivering active pharmaceutical ingredients. Herein we have provided a fast extrusion method to prepare liposomes incorporated with a DNA hydrogel (hydrogel-LNPs) to improve the stability of the LNPs. Taking advantage of the good cellular uptake efficiency, we also demonstrated the potential of hydrogel-LNPs in delivering small molecular doxorubicin (Dox) and nucleic acid drugs. This work provides not only highly biocompatible hydrogel-LNPs for aerosol delivery, but also a strategy to regulate the elasticity of LNPs, which will benefit the potential optimization of drug delivery carriers.