Design of <scp>pH</scp> ‐Sensitive Alginate‐Graft‐Poly(2‐Hydroxyethyl Methacrylate) Microparticles for Controlled Paclitaxel Release

ABSTRACT Stimuli‐responsive polymer carriers are widely investigated for applications in controlled drug delivery and cancer therapy. In this work, pH‐sensitive alginate (Alg) based microspheres grafted with poly(2‐hydroxyethyl methacrylate) (Alg‐ g ‐p(HEMA)) were developed for the release of paclitaxel (PTX). The PTX‐loaded microspheres were obtained through an emulsion crosslinking process, and their structural and morphological characteristics were examined by FTIR, UV, TG/DSC, SEM, and XRD analyses. Swelling experiments performed under different pH conditions (1.2, 5.5, and 7.4) revealed the highest swelling ratio at pH 7.4, reaching 320.59%. Drug release studies indicated a clear pH dependence, with a cumulative release of 82.29% after 24 h at pH 7.4. Increasing the amount of incorporated drug resulted in higher release percentages, while higher grafting ratios led to enhanced swelling and drug release. The release kinetics of the microspheres were analyzed using zero‐order, first‐order, Higuchi, and Korsmeyer–Peppas models. Modeling with the Korsmeyer–Peppas equation indicated that anomalous (non‐Fickian) transport was the dominant mechanism in most formulations. Biocompatibility was evaluated using cytotoxicity assays with CCD‐19Lu cells, while anticancer activity was assessed with K‐562 cells. The findings demonstrate that Alg‐ g ‐p(HEMA) microspheres represent a promising pH‐sensitive carrier system for sustained and controlled delivery of PTX.