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Diabetes skin infection is a very common disorder in hyperglycemic patients. This study evaluated the prospective of developing a topical gel formulation of Aloe vera with insulin-loaded nanoemulsion and evaluates its potential for wound healing in diabetic rats. The insulin-loaded nanoemulsion was fabricated using oleic acidtween 80, and polyethylene glycol 400 to achieve nano sized particles. Selected nanoemulsion (NE5) was incorporated in topical gel containing Aloe vera and control (without Aloe vera). The gels were characterized for in vitro, evaluated in vivo by biochemical, wound healing and histopathological analyses. The pharmaceutical properties of prepared gels indicate good spreadability, permeation and stability. The micrographs of gels showed uniform distribution of nano-sized spherical particles inside the macromolecular network of polymeric gels. Glucose and insulin levels in diabetic rats demonstrated significant antidiabetic effect (P < 0.0001) in the insulin treated groups as compared to the positive control. The wound healing effect substantiate the biochemical data as evidenced by greater wound contraction (75% in 15 days) with gel formulation containing insulin and Aloe vera. Histopathological examination revealed marked improvement in the skin histological architecture of treated groups. Skin irritation study signifies the formulated gel is nonirritant and is safe for topical use. This study concludes that Aloe vera with insulin-loaded nanoemulsion showed synergistic effect towards effective healing of the wound in diabetic rats, and could be a promising and effective approach in the treatment of wounds in diabetic patients

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