Microfluidic Optimization of PEI-Lipid Hybrid Nanoparticles for Efficient DNA Delivery and Transgene Expression.

ABSTRACT: Background: Lipid nanoparticles (LNPs) and polyethyleneimine (PEI) have independently been used for DNA complexation and delivery. However, non-ideal gene delivery efficiency and toxicity have hindered their clinical translation. We developed DNA-PEI-LNPs as a strategy to overcome these limitations and enhance DNA delivery and transgene expression. Methods: Three microfluidic mixing protocols were evaluated: (i) LNPs without PEI, (ii) a single-step process incorporating PEI in the organic phase, and (iii) a two-step process with DNA pre-complexed with PEI before LNP incorporation. The influence of DNA/PEI ratios (1:1, 1:2, 1:3) and DNA/lipid ratios (1:10, 1:40) on particle properties and delivery efficiency was examined. Results: In luciferase formulations, higher DNA/

SUBMITTER: Hosseini-Kharat M 

PROVIDER: S-EPMC12030462 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature