Nioplexes encapsulated in supramolecular hybrid biohydrogels as versatile delivery platforms for nucleic acids

Supramolecular hydrogels based on N-protected phenylalanine (Fmoc-Phe-OH) were used to encapsulate non-ionic surfactant vesicles (niosomes). The niosomes consisted of an amphiphilic lipid mixed with polysorbate-80 and electrostatically complexed with a fluorescently labelled oligodeoxynucleotide (FITC-ODN) as a model nucleic acid derivative. The diffusion properties of the supramolecular hydrogel were conveniently tuned by adding a small amount of kappa-carrageenan (<= 1% w/v) as a crosslinking agent. Interestingly, neither cationic niosomes nor the biopolymer additive significantly affected the hydrogelation properties of the amino acid-based low molecular weight (LMW) gelator. In vitro drug release experiments from Fmoc-Phe-OH hydrogels containing cationic niosomes were successfully carried out in the absence and in the presence of kappa-carrageenan. The niosomal ODN liberation in solution was fitted using Higuchi, Korsmeyer-Peppas and Weibull drug release models, showing the prevalence of diffusion mechanisms in each case. Moreover, the time release was easily prolonged by increasing the concentration of kappa-carrageenan. Preliminary transfection studies indicate the suitability of these supramolecular hybrid hydrogels to embed niosomal formulations and, consequently, for being used as tunable delivery vehicles for nucleic acids.