Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation

Abstract

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux - 0.46 ± 0.02 μg/h/cm(2)) was compared with curcumin-loaded EVs (flux - 4.14 ± 0.04 μg/h/cm(2)). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.

Fig. 1

Visualization of EVs by transmission electron microscopy (magnification a ×40,000 and b ×60,000, respectively)

Fig. 2

Particle size distribution of EVs

Fig. 3

Particle size distribution of EVs before extrusion (a) and after extrusion (b)

Fig. 4

DSC of pure curcumin (a), Span 80 (b), phospholipid (c), and EV dispersion (d)

Fig. 5

Comparison of flux and % skin retention of curcumin from different systems

Fig. 6

Release profiles of curcumin from EVs dispersion and the EVs-hydrophilic ointment

Fig. 7

Percent granuloma formation in cotton pellet-induced granuloma test (n = 5). All groups are significantly different from each other (p < 0.05)