Preparing liposomes through frame guided assembly with high-loading functional nucleic acids.

Recently, a frame guided assembly (FGA) has been demonstrated as a robust tool to prepare liposomes with customized morphologies. However, the potential application of FGA liposomes in delivering nucleic acid drugs is still limited by the low payload. In this study, by systemically investigating the correlation between the leading hydrophobic group (LHG) density and the initial detergent concentration, it has been demonstrated that frames with a low LHG density, which may facilitate the increase of the load of the nucleic acid drug, could be guided to form liposomes at low initial detergent concentrations. By capitalizing on this phenomenon, FGA liposomes with a high loading of ASO/siRNA have been successfully prepared and applied to treat pathogenic genes.

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.