Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcumin

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 +/- 3.47 nm, a zeta potential of -33.1 +/- 1.46 mV, an entrapment efficiency of 99.83 +/- 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases. CUR-DP-NLCs gel could accumulate in the hair follicles and enhance drug retention in the skin. Furthermore, CUR-DP-NLCs gel also induced higher anti-inflammation and analgesic effect after topical administration.