Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections

[EN] Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06 (R), a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around-8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 degrees C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and poly-dispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (similar to 53% at 48 h) while artemisinin was quickly released (similar to 100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections. The authors thank MIUR and PON R & amp; I 2014-2022 for supporting the PhD grant number DOT1304004. We acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. This research is part of the ISGlobal's Program on the Molecular Mechanisms of Malaria which is partially supported by the Fundacion Ramon Areces. Fulgheri, F.; Aroffu, M.; Ramírez, M.; Román-Álamo, L.; Peris, JE.; Usach, I.; Nácher Alonso, MA... (2023). Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections. International Journal of Pharmaceutics. 643. https://doi.org/10.1016/j.ijpharm.2023.123195