RESUMO
An attempt was made to formulate nebivolol-loaded microsponge gel to access drug at wound area, incorporated into gel that possess optimum moist wound management environment during later stages of wound closure. Nebivolol, antihypertensive drug, exhibits vasodilating effects via nitric oxide pathway, slows diabetic neuropathy, and restores endothelial function in diabetic wounds. Microsponges were prepared by optimizing independent variables; drug to polymer ratio and internal phase volume and their effects on production yield, entrapment efficiency, and particle size. Formulations of microsponges were evaluated for drug content. Differential scanning calorimetry indicated reduction in crystallinity of NB during the formation of microsponges. In vitro study (drug to polymer 1:4 and 10 ml internal phase volume acetone) showed 80% drug released within 8 h. Spherical and porous microsponges confirmed by scanning electron microscopy were incorporated in the carbopol 934 (2%) gel base. Gel was characterized for pH, viscosity, and drug content. Less spreadability determined by texture analyzer demonstrated viscous nature of gel. In vitro diffusion study revealed entrapped drug in porous microsponges with slow release to heal wound. In vivo study performed using streptozotocin-induced diabetic rats and excision wound model showed wound healing and closure activity within day 10. Histology revealed inflammatory cell infiltrations and neovascularization in granulation tissues, ultimately healing wound. Microsponge gel prolonged drug release due to entrapped form in porous structure of microsponges with significant and fast wound healing and closure in diabetic rats. Microsponges with loaded drug fulfilled accessibility at wound area, while gel provided optimum moist wound management environment during later stages of wound closure.