Cationic lipid-polymer hybrid carrier for delivery of miRNA and peptides

The clinical translation of therapeutic peptides and miRNAs is hindered by challenges such as short half-life, rapid clearance, and high dosage requirements. To address these limitations, cationic polymeric nanoparticles have been explored, but their development is often limited by toxicity and low transfection efficiency. In this study, we present a novel biocompatible delivery system using a combination of cationic and cholesterol-containing polymers to overcome these issues. The system was formulated into nanocomplexes (NCs) for the delivery of C Peptide (CPep) and miRNA-29b (miR29b). The formulation process involved electrostatic complexation of CPep/miR29b with the polymeric carriers, avoiding harsh conditions or chemical modifications. Native-PAGE, gel retardation, and heparin competition assays confirmed stable complexation. Cell uptake and transfection studies showed efficient delivery of both CPep and miR29b via NCs. In vitro models of oxidative and metabolic stress demonstrated enhanced cell viability with CPep NCs compared to free CPep, with increased glutathione and reduced nitric oxide levels. Similarly, miR29b NCs exhibited potent anti-inflammatory effects compared to free miR29b. This study presents a promising polymer-based carrier system for effective peptide and miRNA delivery through electrostatic interactions alone without any chemical reaction involved to preserve the integrity of the therapeutic.