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<p>This study presents a novel chitosan/graphene oxide (CH/GO) nanocomposite hydrogel microbead system for sustained oral delivery of repaglinide (RPG), developed to address the drug’s short biological half-life and dosing frequency limitations. The nanocomposite microbeads were prepared by ionotropic gelation using sodium tripolyphosphate (STPP) as a cross-linker and optimized through a Box–Behnken experimental design. The optimized formulation, RPG@CH/GO<sub>7</sub>, exhibited high drug entrapment efficiency (92.95%) and drug loading (18.34%), attributed to strong nanoscale interactions between RPG, chitosan, and graphene oxide. Structural characterization using FTIR, XRD, and Raman spectroscopy confirmed successful drug incorporation and polymer–nanofiller interactions, while SEM and TEM analyses revealed spherical, well-defined microbeads with uniform drug distribution. Porosity analysis demonstrated that formulations RPG@CH/G<sub>7</sub>, RPG@CH/G<sub>9</sub>, RPG@CH/G<sub>11</sub>, and RPG@CH/G<sub>13</sub> exhibited optimal porosity (65–75%), indicating a well-interconnected internal network favourable for swelling, drug entrapment, and sustained release. The nanocomposite beads showed pH-responsive swelling behaviour, with enhanced swelling under acidic conditions simulating the gastric environment. In vitro release studies revealed a biphasic release profile, with an initial burst followed by sustained release, achieving approximately 87% drug release over 24&#xa0;h, predominantly governed by Fickian diffusion. In vivo antidiabetic evaluation in alloxan-induced diabetic rats demonstrated a significant and sustained reduction in blood glucose levels, comparable to marketed repaglinide therapy, confirming preserved therapeutic efficacy with prolonged action. The formulation remained physicochemically stable for six months under accelerated storage conditions. The network pharmacology analysis provided mechanistic insight, revealing that repaglinide modulates multiple diabetes-associated pathways related to glucose metabolism, inflammatory signalling, and lipid regulation. Long-term in vivo safety and biocompatibility studies are needed to assess potential toxicity, immunogenic responses, and organ accumulation of graphene oxide following prolonged administration.</p> Graphical abstract <p></p>

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Quality by Design optimized Development of Chitosan/Graphene Oxide Nanocomposite Hydrogel Beads via Network Pharmacology for Sustained Delivery of Repaglinide Release in Diabetes Management

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Renu Saharan,
  • Sarvesh K. Paliwal,
  • Randhir Singh,
  • Suresh Kumar,
  • Abhishek Tiwari,
  • Varsha Tiwari

摘要

This study presents a novel chitosan/graphene oxide (CH/GO) nanocomposite hydrogel microbead system for sustained oral delivery of repaglinide (RPG), developed to address the drug’s short biological half-life and dosing frequency limitations. The nanocomposite microbeads were prepared by ionotropic gelation using sodium tripolyphosphate (STPP) as a cross-linker and optimized through a Box–Behnken experimental design. The optimized formulation, RPG@CH/GO7, exhibited high drug entrapment efficiency (92.95%) and drug loading (18.34%), attributed to strong nanoscale interactions between RPG, chitosan, and graphene oxide. Structural characterization using FTIR, XRD, and Raman spectroscopy confirmed successful drug incorporation and polymer–nanofiller interactions, while SEM and TEM analyses revealed spherical, well-defined microbeads with uniform drug distribution. Porosity analysis demonstrated that formulations RPG@CH/G7, RPG@CH/G9, RPG@CH/G11, and RPG@CH/G13 exhibited optimal porosity (65–75%), indicating a well-interconnected internal network favourable for swelling, drug entrapment, and sustained release. The nanocomposite beads showed pH-responsive swelling behaviour, with enhanced swelling under acidic conditions simulating the gastric environment. In vitro release studies revealed a biphasic release profile, with an initial burst followed by sustained release, achieving approximately 87% drug release over 24 h, predominantly governed by Fickian diffusion. In vivo antidiabetic evaluation in alloxan-induced diabetic rats demonstrated a significant and sustained reduction in blood glucose levels, comparable to marketed repaglinide therapy, confirming preserved therapeutic efficacy with prolonged action. The formulation remained physicochemically stable for six months under accelerated storage conditions. The network pharmacology analysis provided mechanistic insight, revealing that repaglinide modulates multiple diabetes-associated pathways related to glucose metabolism, inflammatory signalling, and lipid regulation. Long-term in vivo safety and biocompatibility studies are needed to assess potential toxicity, immunogenic responses, and organ accumulation of graphene oxide following prolonged administration.

Graphical abstract