Enhanced Reepithelization and Dermal Regeneration of a Novel Pongamia Oil Combination Based Chloramphenicol-Coloaded Curcumin Nanoemulsion Fortified with a Chitosan Hydrogel: Statistical Optimization, ex vivo and in vivo Studies

Abstract

Purpose

In the present study, a novel pongamia oil combination-based chloramphenicol (CPL)-coloaded curcumin (CUR) nanoemulsion (NE)-fortified chitosan hydrogel was formulated for effective wound healing.

Methods

The nanoemulsion was optimized by a central composite design. The factors that exhibited a significant (ANOVA) effect on the responses were studied. FT-IR and DSC studies indicated the compatibility of the drugs with excipients. The selected independent variables were Pongamia oil (PO): Tween 80: propylene glycol (PG), stirring time (ST) and sonication time, and the dependent variables selected were globule size and PDI.

Results

The globule size of the formulations F15a & F15b was found to be 280.23 ± 0.21 and 276.45 ± 0.29 nm, with PDIs of 0.390 ± 0.02 and 0.593 ± 0.02 and zeta potentials of -65.43 ± 0.39 and -70.73 ± 0.63 mV, which confirmed the uniform globule size distribution and stability of the formulations. Compared with the plain drugs, formulations F15a and F15b presented a greater zone of inhibition against Staphylococcus aureus (38 & 35 mm) and E. coli (32&29 mm). TEM analysis revealed a nearly spherical shape of the globules that was free from coalescence. The invitro drug release data indicated sustained drug release for up to 72 h. The exvivo drug release rates of F15a and F15b were 92.4% and 95%, respectively, for CPL and 87.6% and 94%, respectively, for CUR at 24th h. Contour plots were used to select the desired batch range. The stability studies indicated that the formulations remained stable at 40 ± 2 °C and an RH of 75 ± 5%. Compared with the control (70.00 ± 0.18%) and standard (92.04 ± 0.84%) groups, the optimized NE-CPL-CUR hydrogel F15a & F15b-treated groups exhibited greater wound contraction (94.44 ± 0.56 & 99.08 ± 0.18%) at the end of 21 days. Histopathological studies revealed better and improved reepithelization and epidermal and dermal regeneration.

Conclusion

The results of the present study demonstrated that the developed NE-CPL-CUR (0.5:1; CPL and CUR) chitosan-based hydrogel provided better wound healing because of the synergistic combination and presence of Pongamia oil in the nanoemulsion.