Curcumin-loaded colloidal carrier system: formulation optimization, mechanistic insight, ex vivo and in vivo evaluation.

Abstract

The present work investigated the topical delivery potential of nanoemulsion gel loaded with curcumin (CR). CR nanoemulsion (CR-NE) was prepared by spontaneous emulsification method using oil (Labrafac PG/glyceryl triacetate), surfactant:cosurfactant (Smix) (tween 80/polyethylene glycol [PEG] 400) and water. The pseudo-ternary phase diagrams were constructed and thermodynamic stability testing was performed. Droplet size and zeta potential were evaluated using photon correlation spectroscopy and transmission electron spectroscopy. Six formulations selected with an average droplet size ≤70±2.72 nm showed a fourfold increase in skin permeation as compared to crude CR solution in oil. The formulation CR-NE4 having a flux of 117.04±2.32 µg/cm2/h and with maximum retention (42.87%) was selected, characterized (droplet size =41.13±3.34 nm and zeta potential =−33.1±1.45 mV), and incorporated into gel using carbopol-980 (1% w/v). Skin dynamics analyzed by confocal laser scanning microscopy showed maximum deposition of CR up to a depth of 86.98 µm and was in concordance with differential scanning calorimetry and Fourier transform infrared spectroscopy studies that confirmed lipid bilayer disruption, enhancing permeation. A 28-day anti-arthritic evaluation (body weight, paw edema, tibiotarsal joint thickness, TNF-α and IL-1β levels, and histopathology) on Freund’s complete adjuvant induced arthritic rat model after topical application of CR-NE gel in Wistar rats demonstrated substantial reversal of arthritic symptoms. Thus, CR-NE gel possesses potential for therapeutic effects locally in inflammatory arthritic disorders with improved topical bioavailability.