Antitumor potential of lipid nanoformulations with natural antioxidants

Abstract

Quercetin (QUE), tannic acid (TA) and ascorbic acid (AA) are among the antioxidants that have demonstrated efficacy in the treatment and prevention of cancer, cardiovascular and neurodegenerative diseases. However, the optimal method of administering these compounds for therapeutic purposes is not well understood, especially when considering their differences in size and solubility. In this context, nanoencapsulation rises as a promising strategy, since this technology could protect active ingredients and maximize their absorption. In this study, the aforementioned antioxidants were encapsulated in a lipid mixture with the objective of developing nontoxic and effective materials for antitumor therapy. The results demonstrated that the compounds were satisfactorily encapsulated in Large Unilamellar Vesicles (LUVs) composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG). The formulations exhibited good homogeneity in average size as well as stability, as investigated by dynamic light scattering and zeta potential measurements. The encapsulation efficiency was as follows: QUE (78.76%) > TA (61.93%) > AA (47.13%). The Korsmeyer-Peppas model was employed to analyze the release kinetics, illustrating that the delivery of antioxidants follows Fick's law. Biological tests using bioactive-loaded LUVs demonstrated that the encapsulation of these antioxidants resulted in low-toxicity formulations. Quercetin-loaded LUVs (QUE-LUVs) stood out among the formulations studied, as tumor cell viability was significantly reduced after treatment with QUE-LUVs when compared to untreated cells. Furthermore, QUE-LUVs exhibited a differential cytotoxic effect between tumor cells and non-tumor cells, suggesting potential applications in anticancer therapy. Aligned with the demand for innovative treatments as well as drug delivery methods that show less toxicity and adverse effects, the approach developed in the present study resulted in formulations with significant potential and versatility, and could serve as a potential mixed lipid-based delivery system in tumor management using antioxidant therapy.