Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel

Abstract

Polyphenon 60 (P60) and curcumin (CUR) were loaded in a single nanoemulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance availability at target organs and to inhibit enzymatic degradation in gastro intestinal tract, vaginal route of administration was explored. P60 + CUR nanoemulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2 nm, polydispersity index of 0.343, and zeta potential of -32.7 mV. Optimized P60+ CUR NE was characterized by stability testing and transmission electron microscopy, and it was observed that NE was stable at 4°C for 30 days and monodisperse in nature with particle size of 195-205 nm. P60+ CUR NE was further formulated as gel and characterized by viscosity, growth curve analysis, and in vitro permeation studies. In vitro drug permeation studies in simulated vaginal media showed maximum permeation (84 ± 0.21%) of curcumin within 5 h and (91 ± 0.16%) of P60 within 8 h. Both the drugs maintained sustained permeation for 12 h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60 + CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60 + CUR NBG dispersed in the kidney and urinary bladder with (3.07 ± 0.15) and (3.35 ± 0.45) percentage per gram after 3 h for P60 and CUR, respectively, and remained active for 12 h. Scintigraphy images suggested that the P60 + CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract, and this observation was in agreement with the biodistribution results.