Intracellular Uptake of Curcumin-Loaded Solid Lipid Nanoparticles Exhibit Anti-Inflammatory Activities Superior to Those of Curcumin Through the NF-κB Signaling Pathway.

Abstract

Curcumin (Cur) is a naturally derived, novel anti-inflammatory agent, but its poor solubility limits its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) to improve its anti-inflammatory activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using emulsification and low-temperature solidification methods. In contrast to free Cur, the particles were well dispersed in aqueous medium, showing a narrow size distribution with a range of 55 : 1.2 nm, a zeta potential value of -26.2 ± 1.3 mV, and a high drug loading efficiency of 37% ± 2.5%. The sustained release of Cur was observed for up to 6 days. The particles displayed enhanced stability in phosphate-buffered saline by protecting the encapsulated Cur against hydrolysis and biotransformation, as well as increasing biocompatibility. Cur-SLNs were more effective than free Cur at reducing the expression levels of several pro- inflammatory mediators, including inflammatory cytokines (IL-6, TNF-α, and IL-1β) and nitric oxide (NO), under in vitro conditions. By Western blotting, we found that Cur-SLNs were more active than free Cur in inhibiting the LPS-induced activation of the inflammatory transcription factor NF-κB through the suppression of IκB kinase activation. Compared to free Cur, Cur-SLNs had an increased intracellular uptake over time (observed after 24 h) in RAW264.7 cells. Moreover, the Cur-SLNs (≥ 20 μM) significantly improved RAW264.7 cell viability by inhibiting apoptosis. Thus, these results demonstrated that SLNs could be used as potential anti-inflammatory drug carriers for the treatment of various chronic diseases.