In vitro anti-cancer activity and pharmacokinetic evaluation of curcumin-loaded lipid nanocapsules

Abstract

In the present work, lipid nanocapsules (LNC) for curcumin (CCM) encapsulation have been developed and optimized. The objective was to increase drug cytotoxicity on 9L glioma cells and drug bioavailability following intravenous administration (IV). Using the phase inversion technique, we obtained 50 nm LNC loaded with CCM (4 and 6 mg/mL) and, due to the hydrophobic nature of the drug, the encapsulation efficiency was very high, being around 90%. Following 48 h of incubation with 9L cells, CCM-loaded LNC were able to reduce the viability of glioma cells resulting in significant twofold lower IC50 in comparison with the free drug solution. Moreover, CCM-loaded LNC induced both the apoptosis of 9L cells and a strong release of ATP. This suggests a cellular uptake of the LNC and an enhanced anti-proliferative effect. In order to evaluate any alteration in the pharmacokinetic behavior of the encapsulated drug, CCM-loaded LNC were injected IV into healthy rats, at a dose of 10 mg/kg. CCM pharmacokinetic studies were carried out quantifying the CCM concentration from the blood of rats, receiving either CCM-loaded LNC or free CCM solution as a control. The results demonstrated that loaded LNC exhibited a significantly higher AUC, Cmax and t1/2 in comparison with the control, while the clearance was strongly reduced. Globally, these results encouraged the use of CCM-loaded LNC to enhance the in vivo therapeutic activity of the drug after systemic administration.