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

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.