Antiproliferative Evaluation of Dextran Polymer-Based Pomegranate Ethanolic Extract

The pomegranate peel represents an important source of secondary metabolites such as hydrolysable ellagitannins, which are recognized for their antioxidant, anticancer and neuroprotective properties. In this work, the freeze-dried pomegranate peel was extracted by a combined mild maceration at room temperature and ultrasonication at 45 °C using ethanol and acetone as green solvents. The ethanol extract, with an extraction yield of 29%, and IC50 (mg/mL) 0.1067 and 0.0414 for DPPH and ABTS, respectively, was incorporated into a polymer based on dextran, using a grafting reaction, to improve its bioavailability and preserve the chemical integrity. In addition, the potential antitumor activity against breast cancer was evaluated based on the existing literature. In vitro studies have demonstrated the safety and biocompatibility of both free pomegranate peel extract (SSE2-L) and its dextran conjugate (SSPD), with no adverse effects on fibroblasts, erythrocytes, or immune cells. Both formulations inhibited the proliferation of breast cancer cell lines (MCF-7, MDA-MB-231) in a concentration- and time-dependent manner, with SSPD consistently showing superior efficacy. This enhanced activity was corroborated by reduced clonogenic growth, G1 cell-cycle arrest, and improved stability and bioactive retention conferred by polymer conjugation. Overall, these findings highlight dextran-conjugated pomegranate polyphenols as promising candidates for next-generation nutraceuticals and phytopharmaceuticals in cancer chemoprevention and adjunctive therapy, with potential applications extending to other biomedical fields and functional foods.