# Co-Release of Cytarabine and Polyphenol-Rich Extract from Polycaprolactone Microparticles Towards Leukemia Therapy

## TL;DR

This study explores using PCL microparticles to deliver leukemia drugs and polyphenols together, aiming to improve treatment effectiveness and reduce side effects.

## Contribution

A novel co-delivery system using PCL microparticles for cytarabine and pecan-derived polyphenols is developed for leukemia therapy.

## Key findings

- PCL microparticles showed sustained and controlled release of both cytarabine and polyphenol-rich extract.
- The formulations demonstrated good cytocompatibility in preliminary cell viability tests.
- Release profiles were successfully modeled, indicating diffusion- and matrix-controlled mechanisms.

## Abstract

Polymer-based drug delivery systems offer robust opportunities to improve chemotherapy performance while mitigating systemic toxicity, a critical challenge in leukemia treatment. In this study, poly(ε-caprolactone) (PCL) microparticles were developed as carriers for the co-delivery of cytarabine (ARA-C), a frontline antileukemic agent, and a pecan-derived polyphenolic extract (PRE) as a complementary bioactive component. Microparticles were prepared by a double emulsion solvent evaporation method and formulated with varying drug and extract loadings. The systems were characterized in terms of morphology, particle size, colloidal properties, encapsulation efficiency, and chemical composition using optical microscopy, scanning electron microscopy, dynamic light scattering, zeta potential analysis, UV–Vis spectroscopy, Folin–Ciocalteu assay, and FTIR spectroscopy. In vitro release studies revealed sustained and formulation-dependent release profiles for both ARA-C and PRE, which were successfully fitted to kinetic models, indicating diffusion- and matrix-controlled release mechanisms. Additionally, preliminary cell viability assays using fibroblasts supported the cytocompatibility of the formulations. The results support the use of PCL-based microparticles as reproducible polymeric systems for the co-encapsulation and controlled release of cytarabine and polyphenol-rich extracts, contributing to the development of combination delivery approaches relevant to leukemia treatment.