Synergistic anticancer effect of polymersome‐encapsulated curcumin and cytarabine: A spectroscopic and theoretical approach.

Das, Debashree; Bhattacharya, Sampurna; Ganguly, Sreshtha; Sur, Runa; Sen, Kamalika

Cytarabine, also known as cytosine arabinoside is an anticancer drug, and it is widely used to treat acute myeloid leukemia (AML). But, clinical efficacy of highly hydrophilic cytarabine is often limited due to its rapid degradation and high biodistribution. Hence, this study aims to enhance the anticancer effect of cytarabine with the help of a naturally occurring polyphenol, curcumin. The interaction between cytarabine and curcumin was established by different spectroscopic techniques like UV–Visible, fluorescence, and Fourier transform infrared (FT‐IR). Molecular interactions were also studied using isothermal calorimetric titrations (ITC) followed by theoretical docking. The involvement of the amine group of cytarabine with the interaction of curcumin has been supported by FT‐IR and docking study. However, the major challenge with curcumin is that, in spite of its several medicinal benefits, poor solubility and bioavailability restricts its potential clinical applications. Hence, polymersome‐encapsulated curcumin (PEC) was prepared for the intravenous application. A two‐fold decrease in IC50 value of cytarabine against HeLa cell line was found in presence of encapsulated curcumin. This was justified on the basis of observed reactive oxygen species enhancement in serum in presence of cytarabine and PEC together, determined using absorption spectroscopy. The enhanced affinity of cytarabine toward DNA‐curcumin complex as compared to free DNA, supported by theoretical study, also validates the increased cytotoxicity of cytarabine in presence of PEC.

ACUTE myeloid leukemia; CYTARABINE; DRUG delivery systems; REACTIVE oxygen species; ANTINEOPLASTIC agents

Journal of Applied Polymer Science, 2024, Vol 141, Issue 41, p1

0021-8995

Academic Journal

10.1002/app.56052