Nanocellulose-gellan cross-linked scaffolds for vaginal delivery of fluconazole

The objective of this research is to formulate lyophilized fluconazole-loaded nanocellulose-gellan scaffolds cross-linked using trisodium trimetaphosphate as a vaginal drug delivery system. The effect of polymers (nanocellulose and gellan gum) and cross-linking agents on drug release and mucoadhesive strength were determined by approaching a two-factor three-level central composite experimental design. The optimal formulation of the fluconazole-loaded cross-linked rice or wheat nanocellulose-gellan based scaffolds comprised of the concentration of polymers (4.91 % w/v or 4.99 % w/v) and trisodium trimetaphosphate (16.43 % w/v or 15.83 % w/v), respectively. The infrared spectra confirmed the cross-linking of nanocellulose and gellan gum while the thermal graph revealed the higher thermal stability of cross-linked scaffolds. The diffractogram of the scaffolds unveiled their amorphous nature while the electron micrographs depict the porous nature of the fluconazole-loaded nanocellulose-gellan scaffolds. The phosphorylated cross-linked nanocellulose-gellan scaffolds represent more swelling (8-fold higher), porosity (>83 %), tensile strength (>34 MPa), and mucoadhesive strength (>1940 mN), and less enzymatic degradation rate over the non cross-linked scaffolds. The optimal batch of cross-linked nanocellulose-gellan scaffolds provided a sustained release of 99 % of fluconazole over 24 h with 1.19-fold higher ex-vivo vaginal permeation over the native scaffolds. In addition, the phosphorylated nanocellulose-gellan based scaffolds exhibit improved antifungal activity and non-cytotoxicity.