The combinative strategy for improving the intestinal stability and cellular absorption of curcumin by enteric coating of the optimized nanostructured lipid carriers

Curcumin (CUR) exhibits various pharmacological activities. However, it has low solubility under acidic conditions and <1 % bioavailability when administered orally because of degradation by metabolic enzymes in the gastrointestinal tract. Given their high encapsulation efficiency and small particle size, nanostructured lipid carriers (NLCs) can improve the physicochemical stability and bioavailability of drugs. However, whether combining NLCs and enteric coatings can improve the physicochemical stability and bioavailability of CUR re-mains unclear. Therefore, we aimed to improve the bioavailability and absorption of CUR by using NLC and Eudragit (R) S100 (EUD). The optimized factors were as follows: total lipid content of 300 mg, liquid lipid/total lipid ratio of 80 %, and surfactant ratio of 1.35 %. In the reproducibility test, CUR-NLC showed a particle size of 157.8 +/- 2.15 nm, a polydispersity index of 0.125 +/- 0.02, and an encapsulation efficiency of 97.5 +/- 0.04 %. It also had final dissolution rates of 26.56 %, 28.45 %, and 23.21 % in simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8), and distilled water (DW), respectively, and approximately 2.7-3 times better drug release than CUR. Meanwhile, EUD-CUR-NLC had final dissolution rates of 58.64 % and 58.37 % in simulated intestinal fluid (pH 6.8) and DW, respectively, and 2.5 times better drug release than CUR-NLC. EUD-CUR-NLC showed a limited drug release of 22.10 % in simulated gastric fluid (pH 1.2), suggesting that EUD coating was successfully performed. Fluorescence microscopy and flow cytometry revealed that CUR-NLC and EUD-CUR-NLC allowed more than 10-fold higher drug absorption than CUR. In the evaluation of antioxidant activity, the IC50 values of the superoxide dismutase activities of CUR, CUR-NLC, and EUD-CUR-NLC were 555.5, 1428.5, and 1190.5 U/mL, respectively. These results indicate that NLC and EUD may serve as novel drug delivery systems to improve the solubility and intestinal release of CUR. Pharmacokinetic studies using animal models are warranted in the future to evaluate the absorption and distribution of drugs in vivo.