Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Abstract

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriersIn order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (C max) , mean residence time (MRT) and total plasma clearance (CL z /F).Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC 50 value of 5.66 vs. 9.81 mg L -1 , respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.Keywords: curcumin, nanostructured lipid carriers, pharmacokinetic, anticancer effects, lung adenocarcinoma Lung cancer is by far the most frequent cause of cancer-related deaths worldwide (1). The effectiveness of chemotherapeutic agents is often limited by the unavoidable toxicity of drug treatment. It is therefore essential to discover potential agents with more efficient therapeutic strategies and less severe side effects for the treatment of lung cancer. Phytochemicals have been gaining increasing attention as chemopreventive agents to treat various diseases, including lung cancer. Curcumin (C 21 H 20 O 6 ), a hydrophobic polyphenol, is an important phytochemical compound that gives the Asian spice turmeric its light yellow color. It is derived from the rhizome of Curcuma longa and has been long used as food color or for medication purposes worldwide, especially in India and other east Asian countries. 77 % curcumin I (diferuloylmethane), 17 % curcumin II (demethoxycurcumin) and 3 % curcumin III (bis-demethoxycurcumin) are the three major constituents of curcumin. Studies have indicated that curcumin has cancer preventive activity, either alone or in combination with other anticancer agents. Curcumin's widespread availability, safety, low cost and multiple cancer fighting functions make it a promising drug for the treatment of numerous cancers, including lung, cervical, breast, hepatic, pancreatic and colon cancer (2-5). The most attractive and vital reason for the therapeutic use of curcumin is its superior safety profile. It has been demonstrated that curcumin has very low toxicity, even at very high doses (6). Nevertheless, native curcumin cannot reach the therapeutic target in a therapeutic concentration because of its low bioavailability. Therefore, curcumin sho...

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