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Background <p>Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for managing inflammatory disorders such as rheumatoid arthritis (RA); however, their long-term use is frequently associated with gastrointestinal (GI) complications, often leading to RA treatment discontinuation. To address this issue, we developed an oral formulation of troxipide (TRO), a pharmaceutical agent with gastroprotective properties, using nanosuspension technology to enhance its GI absorption and therapeutic efficacy.</p> Methods <p>The TRO nanosuspensions (TRO-NP@dis) were prepared by bead milling with methylcellulose (MC) as a stabilizing agent, yielding particles with an average diameter of 148&#xa0;nm. An adjuvant-induced arthritis (AA) rat model, characterized by heightened susceptibility to NSAID-induced GI injury, was employed to assess pharmacokinetics and therapeutic efficacy.</p> Results <p>TRO-NP@dis showed improved dispersibility relative to conventional microparticle dispersions (TRO-MP@dis). Although the viscosities and zeta potentials of TRO-MP@dis and TRO-NP@dis were comparable, the solubility of TRO-NP@dis was markedly higher. Pharmacokinetic studies in rats revealed enhanced retention of TRO in the stomach, jejunum, and ileum following oral administration of TRO-NP@dis compared with TRO-MP@dis. Indomethacin (IND) administration (40&#xa0;mg/kg) significantly increased the mucosal lesion area in AA rats compared to that in controls. However, the co-administration of TRO-NP@dis significantly reduced the lesion areas in the stomach, jejunum, and ileum compared to those in vehicle-treated AA rats, indicating notable protective effects. These findings suggested that TRO-NP@dis confers enhanced mucosal adhesion and retention, leading to improved therapeutic outcomes in patients with IND-induced GI injury.</p> Conclusions <p>This nanosuspension-based delivery system represents a promising approach for mitigating NSAID-related GI complications in patients with RA by increasing local drug concentrations and reducing mucosal damage.</p>

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Troxipide nanosuspensions prevent indomethacin‑induced gastrointestinal lesions in adjuvant-induced arthritis rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月24日

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  • Kazuya Fujimoto,
  • Hiroko Otake,
  • Rie Tanaka,
  • Fumihiko Ogata,
  • Chika Fujii,
  • Naoki Yamamoto,
  • Naohito Kawasaki,
  • Toshihiko Ishizaka,
  • Takeshi Kotake,
  • Noriaki Nagai

摘要

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for managing inflammatory disorders such as rheumatoid arthritis (RA); however, their long-term use is frequently associated with gastrointestinal (GI) complications, often leading to RA treatment discontinuation. To address this issue, we developed an oral formulation of troxipide (TRO), a pharmaceutical agent with gastroprotective properties, using nanosuspension technology to enhance its GI absorption and therapeutic efficacy.

Methods

The TRO nanosuspensions (TRO-NP@dis) were prepared by bead milling with methylcellulose (MC) as a stabilizing agent, yielding particles with an average diameter of 148 nm. An adjuvant-induced arthritis (AA) rat model, characterized by heightened susceptibility to NSAID-induced GI injury, was employed to assess pharmacokinetics and therapeutic efficacy.

Results

TRO-NP@dis showed improved dispersibility relative to conventional microparticle dispersions (TRO-MP@dis). Although the viscosities and zeta potentials of TRO-MP@dis and TRO-NP@dis were comparable, the solubility of TRO-NP@dis was markedly higher. Pharmacokinetic studies in rats revealed enhanced retention of TRO in the stomach, jejunum, and ileum following oral administration of TRO-NP@dis compared with TRO-MP@dis. Indomethacin (IND) administration (40 mg/kg) significantly increased the mucosal lesion area in AA rats compared to that in controls. However, the co-administration of TRO-NP@dis significantly reduced the lesion areas in the stomach, jejunum, and ileum compared to those in vehicle-treated AA rats, indicating notable protective effects. These findings suggested that TRO-NP@dis confers enhanced mucosal adhesion and retention, leading to improved therapeutic outcomes in patients with IND-induced GI injury.

Conclusions

This nanosuspension-based delivery system represents a promising approach for mitigating NSAID-related GI complications in patients with RA by increasing local drug concentrations and reducing mucosal damage.