Chitosan - hyaluronate based polyplexes for the delivery of oligonucleotides: structural properties and intravitreal mobility

Current retinal therapies involving frequent intravitreal injections for the delivery of DNA and RNA nanomedicines are poorly understood since the injected nanomedicines are affected by the interactions with the vitreous humor. Understanding the structural features and interactions of DNA-polymer complexes helps in the development of effective retinal delivery systems for retinal therapies. In this study we investigated polysaccharide-based polyplexes as potential DNA delivery systems. We utilized advanced instrumental methods to study the structure of N-[4-(trimethylammonium)benzyl]-chitosan:DNA:hyaluronate polyplexes and the mechanism of their formation. We found out that DNA oligonucleotides form star-shaped particles with the cationic chitosan derivative. The complexation with hyaluronate leads to the intercalation of hyaluronate molecules into the polyplex structure instead of forming a surface layer. Obtained polyplexes were tested ex vivo for mobility in porcine vitreous. Both cationic and anionic formulations demonstrated promising mobility that was comparable with anionic and neutral liposomes.