Abstract
Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin.
Highlights
Introduction conditions of the Creative CommonsWounds are physical injuries, leading to an opening or break of the skin [1]
400 are selected as favorable surfactant mixture (Smix) phases based on the desirability of curcumin solubility
It is a widely accepted Smix combination utilized in pharmaceutical products and compatible with the skin
Summary
Wounds are physical injuries, leading to an opening or break of the skin [1]. The appropriate healing of wounds is vital for the repair of disrupted anatomical and functional status of the skin. Topical application of curcumin has been shown to improve the wound healing process and prevent oxidative damage to tissues [8,9]. The poor aqueous solubility of curcumin limits its skin permeation through the stratum corneum (SC), and poses a major limitation on its topical application in wound healing. There is a need for a topical delivery formulation that enhances the water solubility of curcumin, which promotes its permeation through the skin. The NE-based formulation for topical delivery of curcumin increases drug concentrations at the area treated, drug-loading capacity, improves skin penetrability, and prolongs the amount of drug release and those properties helpful for successful wound healing [13,14]. The in vivo wound healing property of the developed formulation was evaluated on rat model and the speed of healing was compared to silver sulfadiazine cream, a common wound healing formulation available in the market
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