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<p>A pH-responsive interpenetrating polymer network (IPN) hydrogel was developed using xanthan gum (XG), carboxymethylcellulose (CMC), and acrylic acid (AA) crosslinked with N, N′-methylenebisacrylamide (MBA) to enhance oral delivery of ticagrelor (TGR)—a BCS Class IV antiplatelet drug with low solubility (10–15&#xa0;μg/mL) and bioavailability (≈36%). The optimized formulation (F5) achieved 90.4 ± 0.52% drug entrapment efficiency and exhibited pH-triggered swelling, demonstrating a 2.41-fold higher equilibrium swelling ratio at pH 6.8 (13.02 ± 0.41) versus pH 1.2 (5.41 ± 0.32; p &lt; 0.001). In vitro release studies revealed pH-dependent sustained release: 86.83% cumulative drug release at pH 6.8 over 24&#xa0;h compared to 47.85% at pH 1.2 (p &lt; 0.001). Release kinetics followed anomalous (non-Fickian) diffusion (Korsmeyer–Peppas model; R<sup>2</sup> &gt; 0.91, n = 0.47–0.59), indicating coupled diffusion/polymer relaxation. FTIR, DSC/TGA, and PXRD confirmed covalent crosslinking, thermal stability (&gt; 200&#xa0;°C), and amorphous drug dispersion, while SEM revealed a porous microstructure. Acute oral toxicity studies (OECD 423; mice (Balb/c), 2&#xa0;g/kg) showed no significant alterations in hematological/biochemical parameters (p &gt; 0.05) or histopathology, affirming safety. This engineered IPN hydrogel effectively addresses the critical solubility limitations of ticagrelor through pH-triggered swelling and sustained release, while demonstrating safety in acute toxicity studies, presenting a highly promising strategy for enhancing its oral therapeutic efficacy in acute coronary syndrome.</p>

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Smart pH-responsive hydrogel for oral delivery of ticagrelor: in vitro characterization and safety assessment of a promising strategy for antiplatelet therapy

  • 期刊论文

  • 发表日期：

    2026年3月31日

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  • Alina Javaid,
  • Nadia Shamshad Malik,
  • Ume Ruqia Tulain,
  • Alia Erum,
  • Ayesha Rashid,
  • Arshad Mahmood,
  • Mohammed S. Alqahtani,
  • Sohail Akram,
  • Asmaa Jabeen,
  • Sajjad Hussain

摘要

A pH-responsive interpenetrating polymer network (IPN) hydrogel was developed using xanthan gum (XG), carboxymethylcellulose (CMC), and acrylic acid (AA) crosslinked with N, N′-methylenebisacrylamide (MBA) to enhance oral delivery of ticagrelor (TGR)—a BCS Class IV antiplatelet drug with low solubility (10–15 μg/mL) and bioavailability (≈36%). The optimized formulation (F5) achieved 90.4 ± 0.52% drug entrapment efficiency and exhibited pH-triggered swelling, demonstrating a 2.41-fold higher equilibrium swelling ratio at pH 6.8 (13.02 ± 0.41) versus pH 1.2 (5.41 ± 0.32; p < 0.001). In vitro release studies revealed pH-dependent sustained release: 86.83% cumulative drug release at pH 6.8 over 24 h compared to 47.85% at pH 1.2 (p < 0.001). Release kinetics followed anomalous (non-Fickian) diffusion (Korsmeyer–Peppas model; R2 > 0.91, n = 0.47–0.59), indicating coupled diffusion/polymer relaxation. FTIR, DSC/TGA, and PXRD confirmed covalent crosslinking, thermal stability (> 200 °C), and amorphous drug dispersion, while SEM revealed a porous microstructure. Acute oral toxicity studies (OECD 423; mice (Balb/c), 2 g/kg) showed no significant alterations in hematological/biochemical parameters (p > 0.05) or histopathology, affirming safety. This engineered IPN hydrogel effectively addresses the critical solubility limitations of ticagrelor through pH-triggered swelling and sustained release, while demonstrating safety in acute toxicity studies, presenting a highly promising strategy for enhancing its oral therapeutic efficacy in acute coronary syndrome.