Enhanced delivery of anti-inflammatory miRNA-497 to dermal fibroblasts using cationized gelatin-sodium alginate coacervates

MiRNAs have emerged as promising therapeutics for a wide array of diseases, prompting exploration into various gene delivery systems to enhance their cellular uptake and stability. This study aimed to devise a biocompatible delivery system for miR-497 utilizing coacervates, which are dense liquid phases formed via electrostatic interactions between oppositely charged polymers. We evaluated the complex coacervation of low and high molecular weight cationized gelatin (LWCG and HWCG) with sodium alginate (SA) to encapsulate miRNA. First, we examined the impact of the CG/SA ratio on turbidity and zeta potential. Positive zeta potentials were observed at CG/SA ratios of 1: 0 and 1: 0.2 for both LWCG and HWCG, guiding our Design of Experiments (DoE) to optimize the CG/SA coacervates for miR-497 encapsulation. The resulting optimized coacervates (LWCG/SA ratio of 1:0.05 and HWCG/SA ratio of 1:0.09) effectively delivered miR-497 to human dermal fibroblasts (HDF) and keratinocytes without inducing cytotoxicity. Moreover, these coacervates demonstrated a reduction in pro-inflammatory cytokines in HDF cells under hyperglycemic conditions. Taken together, our findings underscore the potential of a delivery system comprising miRNA-loaded CG/SA coacervates as a promising topical treatment for chronic wounds such as diabetic foot ulcers.