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<p>Diosmetin (DIO) is a bioflavonoid derived from citrus fruits and herbs that exhibits antibacterial, antioxidant, anticancer and anti-inflammatory properties with potential applications for neurodegenerative diseases. However, its limited water solubility and low bioavailability restrict its therapeutic efficacy. To improve DIO solubility, the inclusion complexes (ICs) with β-Cyclodextrin (β-CD) were synthesized and evaluated for drug release. The phase solubility study determined the IC stoichiometry and complexation constant (232.3&#xa0;M⁻<sup>1</sup>) with an AL-type curve. DIO: β-CD ICs were prepared using physical (PM), kneading (KM) and microwave (MW) methods in a 1:1 ratio and characterized using FTIR, P-XRD, SEM, DSC, <sup>1</sup>H NMR and 2D NMR ROESY. The pH-responsive PA-CMC-HPN hydrogel crosslinked with epichlorohydrin (ECH) was synthesized under microwave conditions and optimized using Response Surface Methodology (RSM) to achieve maximum percentage swelling (2245%). Further, the DIO:β-CD ICs were incorporated into the hydrogel matrix for controlled release under physiological conditions (37&#xa0;°C). In vitro studies, the release of DIO at pH 2, 7 and 7.4 revealed that MW ICs exhibit the highest release efficiency. After 24&#xa0;h, the cumulative DIO release was 89.02&#xa0;ppm at pH 2, 92.32&#xa0;ppm at pH 7 and 94.45&#xa0;ppm at pH 7.4. The release kinetics studies followed the Korsmeyer-Peppas and Peppas-Sahlin models, demonstrating a diffusion-dominated transport mechanism. This study highlights β-CD’s role in enhancing DIO solubility and the potential of the PA-CMC-HPN matrix as a controlled-release system.</p> Graphic abstract <p></p>

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β-cyclodextrin mediated controlled release of diosmetin from ph-responsive pullulan-carboxymethyl cellulose hydrogel optimized through experimental design

  • 期刊论文

  • 发表日期：

    2025年8月29日

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  • Rahul,
  • Rajeev Jindal

摘要

Diosmetin (DIO) is a bioflavonoid derived from citrus fruits and herbs that exhibits antibacterial, antioxidant, anticancer and anti-inflammatory properties with potential applications for neurodegenerative diseases. However, its limited water solubility and low bioavailability restrict its therapeutic efficacy. To improve DIO solubility, the inclusion complexes (ICs) with β-Cyclodextrin (β-CD) were synthesized and evaluated for drug release. The phase solubility study determined the IC stoichiometry and complexation constant (232.3 M⁻1) with an AL-type curve. DIO: β-CD ICs were prepared using physical (PM), kneading (KM) and microwave (MW) methods in a 1:1 ratio and characterized using FTIR, P-XRD, SEM, DSC, 1H NMR and 2D NMR ROESY. The pH-responsive PA-CMC-HPN hydrogel crosslinked with epichlorohydrin (ECH) was synthesized under microwave conditions and optimized using Response Surface Methodology (RSM) to achieve maximum percentage swelling (2245%). Further, the DIO:β-CD ICs were incorporated into the hydrogel matrix for controlled release under physiological conditions (37 °C). In vitro studies, the release of DIO at pH 2, 7 and 7.4 revealed that MW ICs exhibit the highest release efficiency. After 24 h, the cumulative DIO release was 89.02 ppm at pH 2, 92.32 ppm at pH 7 and 94.45 ppm at pH 7.4. The release kinetics studies followed the Korsmeyer-Peppas and Peppas-Sahlin models, demonstrating a diffusion-dominated transport mechanism. This study highlights β-CD’s role in enhancing DIO solubility and the potential of the PA-CMC-HPN matrix as a controlled-release system.

Graphic abstract