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

Abstract

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.

DNA-based nanostructures for RNA delivery

“…Figure reproduced with permission from Ref. [ 92 ], Copyright 2023, American Chemical Society: Danvers, MA, USA.…”

“…This innovative strategy allowed for the stable delivery of both small molecule doxorubicin and nucleic acid drugs such as siRNAs, resulting in efficient induction of apoptosis in lung adenocarcinoma cells. The nebulized lipid nanoparticles carrying siRNA IGF1R demonstrated promising potential for cancer therapy ( Figure 5D ) [ 92 ]. The controllable release of nucleic acid drugs at target sites by DNA-based hydrogel has shown safe and effective delivery of nucleotide acid therapy, leading to significant improvement in immunity activation and tumor suppression.…”

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology

“…[7][8][9][10][11][12][13] The advantages of the use of NMeds are even more evident with the advancement of gene therapeutics where the genetic material must be well protected from the immune system, delivered to the site of interest with high specificity, enter into the cell, and arrive at the point of interest (nucleus or cytoplasm) in a sufficient amount for a therapeutic effect. [14][15][16][17] In fact, when discussing DNA delivery, and/or its co-delivery with other molecules such as siRNA, great strides have already, and still are, being made demonstrating these capabilities in a variety of NMed systems ranging from dendrimers, [18][19][20][21][22] inorganic, [23][24][25] polymeric, [26][27][28][29][30][31] and lipidic [32][33][34][35][36] nanoparticles which were able to protect, target, and effectively transfect genes in in vitro studies. Cationic charges have been primarily used to stabilize the DNA through charge interaction in order to protect the plasmid DNA being delivered, even though the charge interaction with cell surface proteins was correlated to cell toxicity.…”