Thermoresponsive in situ gel of curcumin loaded solid lipid nanoparticle: Design, optimization and in vitro characterization

Owing to the antioxidant, anti-inflammatory, amyloid inhibition, and neuroprotective potency, curcumin proved as an excellent herbal bioactive to treat AD. However, poor solubility, lipophilicity, rapid metabolism, and short half-life restrict its therapeutic efficacy. To improve the physicochemical properties and achieve prolonged release, we have prepared curcumin-loaded SLN (CSL) and optimized via response surface methodology. CSL was prepared by melt emulsification-ultrasonication technique. Experimental design (33 Box-Behnken) suggested 17 runs by taking drug: lipid ratio, concentration of surfactant and sonication time as independent factors whereas the size, %EE and drug release as dependant factors. The optimized formulation was observed with particle size 258.6 +/- 47.39 nm, PDI 0.354 +/- 0.02, zeta potential 19.3 +/- 2.33 mV, and entrapment efficiency 81.49 +/- 1.17%. CSL showed a biphasic release pattern with an initial burst release of 21% drug in 2 h followed by prolonged release of 84.92 +/- 0.79% in 48 h. Weibull kinetic equation was found best fit for the drug release. The release mechanism depicted diffusion-controlled release along with initial surface erosion. Further, the optimized CSL was loaded in poloxamer based thermoresponsive in situ gel which showed good gelation behavior with 30 & PLUSMN; 0.8 C gelation temperature and gelation time 1 min. The DPPH study indicated satisfactory oxidative potency of drug in terms of % RSA. However, we have observed that loading in SLN and in situ gel reduced the antioxidant potency to some extent. Such reduction might be due to the stealth nature and prolonged release behavior of the nanocarrier which restricts the direct exposure of the drug to the reaction mixture.

Automated summary

Curcumin has been shown to have antioxidant, anti-inflammatory, amyloid inhibition, and neuroprotective properties, but its poor solubility, lipophilicity, rapid metabolism, and short half-life limit its efficacy in treating AD. This study developed curcumin-loaded solid lipid nanoparticles (CSL) to improve the physicochemical properties and achieved prolonged release. However, the loading reduced the antioxidant potency of curcumin.