Improved Exposure of Curcumin-Loaded Nanocapsules: Drug Quantification in LPS-Induced Drosophila melanogaster and Pharmacokinetics in Wistar Rats

Ana Cláudia Funguetto-Ribeiro¹Camila Pacheco²Flávia Elizabete Teixeira¹Joane Ferreira¹Eliana Fernandes¹Gustavo Guerra¹Francine Johansson Azeredo³Sandra Haas^1*

• ¹Federal University of Pampa, Bagé, Brazil
• ²Universidade Federal de Santa Maria, Santa Maria, Brazil
• ³University of Florida, Gainesville, United States

Curcumin (CUR) has broad pharmacological potential; however, its clinical efficacy is hindered by low aqueous solubility, extensive presystemic metabolism, and poor oral bioavailability. Nanoencapsulation strategies have been proposed to overcome these limitations. Here, we evaluated the exposure of poly(ε-caprolactone) nanocapsules coated with polysorbate 80 containing CUR (NC-CUR) using a validated bioanalytical approach capable of quantifying this drug in whole-body homogenates of Drosophila melanogaster and in rat plasma. Healthy and LPS-challenged flies were chronically treated with CUR or NC-CUR (37 or 110 ng/mL) for 10 days through dietary exposure. Male Wistar rats received a single intravenous (2 mg/kg) or oral (6 mg/kg) dose of CUR or NC-CUR to characterize systemic pharmacokinetics. In vitro release followed a biexponential profile, with NC-CUR showing significantly prolonged release compared to free CUR (t1/2β = 25.79 ± 0.87 h vs. 3.15 ± 1.37 h; p < 0.0001). A validated HPLC-PDA method (LLOQ = 3 ng/mL; R2 ≥ 0.997) enabled CUR quantification in whole flies and rat plasma. Chronic dietary exposure resulted in markedly higher CUR concentrations in flies treated with NC-CUR than free CUR (up to ~200 vs. 75 ng/mL; p < 0.001), including under LPS-induced inflammatory conditions. In rats, NC-CUR increased systemic exposure following both intravenous (AUC0-∞: 1337.8 ± 385.2 vs. 100.4 ± 24.4 h·ng/mL; 13.3-fold, p < 0.0001) and oral administration (82.23 ± 31.68 vs. 25.55 ± 7.17 h·ng/mL; 3.2-fold, p < 0.01), reduced clearance (0.57 ± 0.18 vs. 7.71 ± 1.81 L/h; p < 0.0001), and accelerated absorption after oral dosing (Tmax: 0.58 ± 0.12 vs. 1.31 ± 0.28 h; p < 0.05). In conclusion, nanoencapsulation significantly enhanced CUR exposure in both invertebrate and mammalian systems. This cross-species analytical strategy supports D. melanogaster as a complementary quantitative platform for early pharmacokinetic screening and reinforces NC-CUR as a promising formulation for future translational development in inflammatory conditions.