Folic acid-functionalized nanoemulsion of exemestane and quercetin: targeting breast cancer through receptor-mediated uptake and improved pharmacokinetics

Abstract

Poor bioavailability and systemic toxicity restrict the oral administration of chemotherapeutic agents such as exemestane (EXM) and quercetin (QUR). Targeted nanoformulations have the potential to enhance therapeutic efficacy and safety. This study focused on preparing and optimizing folic acid (FA)-conjugated EXM and QUR-loaded nanoemulsion (EXM-QUR-FA-NE) for breast cancer.

Using Capryol-90 (1.5% v/v), Smix (3% v/v), and a sonication period of 50 s, the formulation was optimized that showed droplet size (168.3 ± 3.1 nm), PDI (0.194 ± 0.015), and zeta potential (20.52 ± 2.27 mV). The ex vivo permeation analysis demonstrated a 2.28-fold and 2.45-fold better permeation of EXM and QUR, respectively, from EXM-QUR-FA-NE, aligning with CLSM results, which showed 1.66-fold deeper tissue penetration.

In pH 1.2, EXM-QUR-FA-NE exhibited a significantly lower drug release, whereas a sustained release pattern was observed in pH 6.8 from EXM-QUR-FA-NE. In vitro cytotoxicity on MCF-7 cells confirmed strong anticancer potential, exhibiting cell inhibition and a low IC₅₀. Pharmacokinetic studies exhibited a 2.94-fold increase in AUC for EXM and a 3.47-fold increase for QUR, indicating prolonged systemic circulation.

Additionally, acute toxicity studies showed reduced histopathological alterations in liver, kidney, and breast tissues. EXM-QUR-FA-NE emerges as a promising oral delivery approach for targeted breast cancer therapy, ensuring enhanced delivery, sustained release, improved bioavailability, and reduced toxicity.

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Following excipients are mentioned in the study besides other: Capryol-90

Qizilbash, F. F., Nehal, N., A. Emad, N., Sartaj, A., Alam, O., Baboota, S., … Ali, A. (2025). Folic acid-functionalized nanoemulsion of exemestane and quercetin: targeting breast cancer through receptor-mediated uptake and improved pharmacokinetics. Journal of Dispersion Science and Technology, 1–25. https://doi.org/10.1080/01932691.2025.2556683

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