Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing
An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml.
Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing.
αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.
Conclusions
Chitosan oleate (CS-OA) appears suitable to stabilize NEs loaded with αTph, that are easily dispersible in aqueous media and therefore in wound fluids. The bioactive properties of both chitosan and oleic acid make the amphiphilic polymer especially useful for the encapsulation of αTph aimed to wound healing. The evaluation of the unloaded CS-OA and of the αTphNE systems, performed on cell cultures of fibroblasts and keratinocytes and on ex vivo human skin biopsies, confirm a proliferative effect on both cell lines and on biopsies especially for αTph loaded nanoemulsions, but also for unloaded CS-OA.
In the perspective of the design of a drug delivery system suitable for the NE administration to wounds and burns, a spray drying process was developed by means of a response surface DOE approach to optimize yield and αTph loading in a cutaneous powder. The stability of αTph, improved after encapsulation, was further increased by spray drying the nanoemulsion. This pointed out the possibility to formulate the nanoemulsion in Trojan microparticles, for which good antioxidant ability was assessed. The release of αTph from this powder, complete in a few hours, resulted compatible with a possible daily application in wound or burn treatment.
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