Impact of PEGylation and hyaluronan functionalization on lipoplex-mediated mRNA delivery to the canine retina.

ABSTRACT: Efficient messenger ribonucleic acid (mRNA) delivery to the retina remains challenging. This study investigated the effects of various polyethylene glycol (PEG) derivatives on the stability and uptake of cationic lipid-based mRNA lipoplexes in vitro and assessed the delivery of selected formulations to the canine retina. We present an optimized workflow for formulating mRNA lipoplexes in pure water, achieving high encapsulation efficiency. PEGylation enhanced stability of lipoplexes, particularly with PEG-DMG or hyaluronan conjugated to PEG-DPPE (HA-PEG-DPPE), maintaining size and zeta potential for 48 hours. RNA in situ hybridization (RNA-ISH) confirmed efficient internalization of PEGylated mRNA lipoplexes by cultured RAW264.7 and ARPE19 cells, though corresponding protein

SUBMITTER: Appelbaum T 

PROVIDER: S-EPMC12351706 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature