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. 2025 Jul 16;42(8):335.
doi: 10.1007/s12032-025-02880-5.

Design and evaluation of casein nanoparticles for co-delivery of curcumin and fluorouracil acetic acid in cancer therapy

Aman Chaudhary  1 , Ashok Behera  2 , Jagannath Sahoo  3   4
Affiliations

Design and evaluation of casein nanoparticles for co-delivery of curcumin and fluorouracil acetic acid in cancer therapy

Aman Chaudhary et al. Med Oncol. .

Abstract

Poor aqueous solubility and permeability hinder the therapeutic potential of curcumin (CUR) and fluorouracil acetic acid (FUA), limiting their clinical translation despite their anticancer properties. This study aimed to address these challenges by developing a novel casein nanoparticle system (CUR-FUA NPs) optimized for enhanced synergistic efficacy. The formulation was optimized by evaluating drug loading and entrapment efficiency, ensuring the effective incorporation of CUR and FUA, with drug loading of 54.2% and entrapment efficiency of 21.4% and 96.45%, respectively, for FUA and CUR. The optimized nanoparticles exhibited favorable physicochemical properties, including uniform size distribution of 182.34 ± 22.36 nm, surface morphology, and structural integrity, as characterized by dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Entrapment efficiency studies confirmed efficient drug encapsulation, while in vitro cytotoxicity assays demonstrated potent anticancer activity. Ex vivo permeation studies validated improved drug absorption, and physiological and serum stability assessments confirmed nanoparticle integrity. Additionally, hemocompatibility assays, which showed hemolysis around 3.5% at 500 µg/ml concentration, ensured the biocompatibility of the developed system. Antioxidant activity assays, including free radical scavenging evaluations, revealed enhanced antioxidant potential due to the synergistic effects of CUR and FUA with IC50 of CUR and CUR-FUA NPs at 41.303 μg/ml and 31.82 μg/ml, respectively, for DPPH assay and IC50 at 25.15 μg/ml and 22.5 μg/ml, respectively, for ABTS assay. In vitro drug release studies, supported by release kinetic modeling, exhibited pH-responsive behavior, with enhanced drug release at acidic pH (5.5 and 6.8), favoring selective cancer cell targeting. This study highlights the successful development of CUR-FUA NPs as a promising co-delivery system with improved solubility, stability, biocompatibility, and synergistic anticancer efficacy, suggesting potential pharmaceutical applications for enhanced cancer treatment.

Keywords: 5-Fluorouracil acetic acid; Antioxidant study; Co-delivery; Curcumin; Hemolysis; In vitro study.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Consent for publication: Not applicable. Ethical approval: Not applicable. Humans and animals rights: The research does not involve humans or animals. Informed consent: All authors consent to the publication of this article.

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