Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo

CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC(0–)(t)) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.