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<p>The objective of this research was to improve the brain bioavailability of Sesamol (SAL) via formulating novel-chitosan (CHIT)-coated PLGA-nanoparticles and quantifying SAL using a novel LC-MS/MS analytical approach. The approach was evaluated for its potential in treating ischemic brain injury and colorectal cancer. PLGA-based nanoparticles encapsulating sesamol (NPs) were produced through the emulsion-based solvent evaporation approach, followed by surface coating with chitosan. The chitosan-coated Sesamol-PLGA NPs were optimized based on characteristics including particle dimensions, encapsulation efficiency, zeta potential, PDI, and drug encapsulation efficiency. Characterization was conducted along with in vitro release of the drug and its permeation through the nasal membrane studies to assess their potential for enhancing brain bioavailability. Additionally, neurobehavioral assessments, biochemical analyses, and histopathological evaluations were performed. The anticancer potential of CHIT-SAL-PLGA NPs was further tested against HT-29, a human Colorectal-cancer cell line. The optimized CHIT-SAL-PLGA NPs exhibited a particle-size of 56.02 ± 2.74&#xa0;nm, PDI of 0.233 ± 0.008, zeta potential of − 15.4 ± 1.04 mV, drug loading of 29.65 ± 3.64%, and entrapment efficiency of 80.09 ± 6.03%. They demonstrated sustained, controlled drug release (84.97 ± 7.08%) and high permeation efficiency (&gt; 84.21%). Sesamol showed a retention-time of 1.650&#xa0;min with m/z 137/109, and the LC-MS/MS method displayed excellent linearity (0.50–1900 ng/mL), with intra- and interday CV values of 1.10–2.04% and 1.08–1.97%, and accuracy of 96.83–98.39% and 96.63–98.87%, respectively. Intranasal administration of CHIT-SAL-PLGA NPs significantly increased AUC₀–₂₄ and Cmax (<i>p</i> &lt; 0.001) compared to controls. In ischemic MCAO rat models, these nanoparticles produced marked improvements in biochemical, neurobehavioral, and histopathological parameters. In vitro cytotoxicity studies revealed enhanced anticancer activity against HT-29 colorectal cancer cells (IC₅₀ = 695.28 µM) compared to pure Sesamol (IC₅₀ = 1391.26 µM). The study demonstrated that CHIT-SAL-PLGA NPs significantly improved the brain bioavailability of Sesamol through intranasal transport in rats, enabling efficient targeting to the brain for cerebral ischemia treatment. This approach improved neuroprotection while requiring only a minimal dose of Sesamol. Moreover, the optimized CHIT-SAL-PLGA NPs exhibited markedly greater anticancer activity (<i>p</i> &lt; 0.01) against HT-29 human colorectal cancer cells compared to free Sesamol.</p>

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Engineering of sesamol-integrated polymeric nanoparticles for enhanced therapeutic outcomes in cancer and cerebral ischemia

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Niyaz Ahmad,
  • Mohammad Rashid,
  • Zabih Ullah,
  • Naseem Akhtar,
  • Md Makhmur Ahmad,
  • Md Tanwir Athar,
  • Shamshir Khan,
  • Mohd Faiyaz Khan,
  • Sarfaraz Ahmad

摘要

The objective of this research was to improve the brain bioavailability of Sesamol (SAL) via formulating novel-chitosan (CHIT)-coated PLGA-nanoparticles and quantifying SAL using a novel LC-MS/MS analytical approach. The approach was evaluated for its potential in treating ischemic brain injury and colorectal cancer. PLGA-based nanoparticles encapsulating sesamol (NPs) were produced through the emulsion-based solvent evaporation approach, followed by surface coating with chitosan. The chitosan-coated Sesamol-PLGA NPs were optimized based on characteristics including particle dimensions, encapsulation efficiency, zeta potential, PDI, and drug encapsulation efficiency. Characterization was conducted along with in vitro release of the drug and its permeation through the nasal membrane studies to assess their potential for enhancing brain bioavailability. Additionally, neurobehavioral assessments, biochemical analyses, and histopathological evaluations were performed. The anticancer potential of CHIT-SAL-PLGA NPs was further tested against HT-29, a human Colorectal-cancer cell line. The optimized CHIT-SAL-PLGA NPs exhibited a particle-size of 56.02 ± 2.74 nm, PDI of 0.233 ± 0.008, zeta potential of − 15.4 ± 1.04 mV, drug loading of 29.65 ± 3.64%, and entrapment efficiency of 80.09 ± 6.03%. They demonstrated sustained, controlled drug release (84.97 ± 7.08%) and high permeation efficiency (> 84.21%). Sesamol showed a retention-time of 1.650 min with m/z 137/109, and the LC-MS/MS method displayed excellent linearity (0.50–1900 ng/mL), with intra- and interday CV values of 1.10–2.04% and 1.08–1.97%, and accuracy of 96.83–98.39% and 96.63–98.87%, respectively. Intranasal administration of CHIT-SAL-PLGA NPs significantly increased AUC₀–₂₄ and Cmax (p < 0.001) compared to controls. In ischemic MCAO rat models, these nanoparticles produced marked improvements in biochemical, neurobehavioral, and histopathological parameters. In vitro cytotoxicity studies revealed enhanced anticancer activity against HT-29 colorectal cancer cells (IC₅₀ = 695.28 µM) compared to pure Sesamol (IC₅₀ = 1391.26 µM). The study demonstrated that CHIT-SAL-PLGA NPs significantly improved the brain bioavailability of Sesamol through intranasal transport in rats, enabling efficient targeting to the brain for cerebral ischemia treatment. This approach improved neuroprotection while requiring only a minimal dose of Sesamol. Moreover, the optimized CHIT-SAL-PLGA NPs exhibited markedly greater anticancer activity (p < 0.01) against HT-29 human colorectal cancer cells compared to free Sesamol.