Co–encapsulation of flavonoids with anti–cancer drugs: a challenge ahead

Flavonoids have been considered as promising molecules for cancer treatment due to their pleiotropic properties such as anti–carcinogenic, anti–angiogenic or efflux proteins inhibition. However, due to their lipophilic properties and their chemical instability, vectorization seems compulsory to administer flavonoids. Flavonoids have been co-encapsulated with other anti-cancer agents in a broad range of nanocarriers aiming to i) achieve a synergistic/additive effect at the tumor site, ii) delay drug resistance apparition by combining agents with different action mechanisms or iii) administer a lower dose of the anti-cancer drug, reducing its toxicity. However, co-encapsulation could lead to a change in the nanoparticles’ diameter and drug-loading, as well as a decrease in their stability during storage. The preparation process should also take into accounts the physico-chemical properties of both the flavonoid and the anti-cancer agent. Moreover, the co-encapsulation could affect the release and activity of each drug. This review aims to study the formulation, preparation and characterization strategies of these co-loaded nanomedicines, as well as their stability. The in vitro assays to predict the nanomedicines’ behavior in biological fluids, as well as their in vivo efficacy, are also discussed. A special focus concerns the evaluation of their synergistic effect on tumor treatment.

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Morgane Renault–Mahieux, Nathalie Mignet, Johanne Seguin, Khair Alhareth, Muriel Paul, Karine Andrieux,
Co–encapsulation of flavonoids with anti–cancer drugs: a challenge ahead,
International Journal of Pharmaceutics, 2022, 121942, ISSN 0378-5173,

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