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<p>Ganciclovir is a poorly bioavailable drug. The objective of this study was to formulate chitosan nanoparticles to improve intestinal permeability. Ganciclovir-loaded chitosan nanoparticles were optimized using the Box-Behnken design. The pH, chitosan-TPP ratio, and chitosan concentration were used as independent variables. The particle size, % entrapment efficiency, and % drug release was used as response parameters to optimize the nanoparticles. Scanning electron microscopy was used to determine the shapes of the optimized nanoformulations. Ex vivo permeation studies were performed using different parts of the chicken intestine, such as the duodenum, jejunum, and ileum. The particle sizes, % entrapment efficiency, and % drug release of chitosan nanoparticles ranged from 217.5&#xa0;nm to 432.9&#xa0;nm, 60.02 to 77.9%, and 74.7 to 91.6%, respectively. Ganciclovir-loaded chitosan nanoparticles prepared at pH 5.4, chitosan-TPP ratio of 2:1, and chitosan concentration of 2% exhibited the smallest particle size, highest, and highest % entrapment efficiency, and % drug release. Sanning electron microscopy analysis showed spherical nanoparticles that were uniform in shape. In silico ADME predictions indicated poor permeability and rapid clearance of ganciclovir, supporting its low bioavailability profile. The permeability coefficient of chitosan nanoparticles from the ileum was significantly higher than that from the duodenum and jejunum. The permeability coefficient of chitosan nanoparticles in the ileum (4.46 × 10⁻<sup>6</sup> cm/s) was significantly higher than that in the duodenum (3.38 × 10⁻<sup>6</sup>cm/s) and jejunum (2.8 × 10⁻<sup>6</sup> cm/s). This study concluded that chitosan nanoparticles enhanced the intestinal permeability of Ganciclovir, thereby improving its oral bioavailability.</p>

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Formulation and Optimization of Ganciclovir-Loaded Chitosan-Tripolyphosphate Nanoparticles: In Silico Pharmacokinetic Prediction and Ex Vivo Intestinal Permeation Studies

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Prachi Sharma,
  • Sourin Bhukta,
  • Narahari N. Palei,
  • Anuradha Mishra,
  • Vijayaraj Surendran,
  • Lucy Mohapatra

摘要

Ganciclovir is a poorly bioavailable drug. The objective of this study was to formulate chitosan nanoparticles to improve intestinal permeability. Ganciclovir-loaded chitosan nanoparticles were optimized using the Box-Behnken design. The pH, chitosan-TPP ratio, and chitosan concentration were used as independent variables. The particle size, % entrapment efficiency, and % drug release was used as response parameters to optimize the nanoparticles. Scanning electron microscopy was used to determine the shapes of the optimized nanoformulations. Ex vivo permeation studies were performed using different parts of the chicken intestine, such as the duodenum, jejunum, and ileum. The particle sizes, % entrapment efficiency, and % drug release of chitosan nanoparticles ranged from 217.5 nm to 432.9 nm, 60.02 to 77.9%, and 74.7 to 91.6%, respectively. Ganciclovir-loaded chitosan nanoparticles prepared at pH 5.4, chitosan-TPP ratio of 2:1, and chitosan concentration of 2% exhibited the smallest particle size, highest, and highest % entrapment efficiency, and % drug release. Sanning electron microscopy analysis showed spherical nanoparticles that were uniform in shape. In silico ADME predictions indicated poor permeability and rapid clearance of ganciclovir, supporting its low bioavailability profile. The permeability coefficient of chitosan nanoparticles from the ileum was significantly higher than that from the duodenum and jejunum. The permeability coefficient of chitosan nanoparticles in the ileum (4.46 × 10⁻6 cm/s) was significantly higher than that in the duodenum (3.38 × 10⁻6cm/s) and jejunum (2.8 × 10⁻6 cm/s). This study concluded that chitosan nanoparticles enhanced the intestinal permeability of Ganciclovir, thereby improving its oral bioavailability.