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Purpose <p>This research aims to develop a pulmonary delivery system of axitinib (AXT) as a spray-dried microparticle to address its poor solubility, variable oral bioavailability, and systemic adverse effects, thereby enhancing its potential application in LC therapy.</p> Methods <p>The microparticles were produced via spray drying using lactose and L-leucine as stabilizing carriers. The spray drying was carried out at an inlet/outlet temperature of 105&#xa0;°C/60 °C, and feed rate of 2 mL/min. The formulations were characterized for production yield, drug content, solid-state analysis using DSC, PXRD, FTIR, morphology by SEM, aerosolization efficiency, and in vitro cytotoxicity activity against A549 lung carcinoma cells. Further, the stability of the optimized formulation was examined under accelerated conditions at 40&#xa0;°C ± 2&#xa0;°C and 75% ± 5% RH.</p> Results <p>Among the prepared formulations, the D6 formulation (84.56% of lactose, and 14.71% of L-leucine) demonstrated the most desirable performance, showing a high emitted dose (98.42%) and fine particle fraction (44.33%) with an MMAD of 2.11&#xa0;μm. The solid-state studies confirmed the transformation of AXT into an amorphous form, improving the solubility of AXT. SEM images revealed smooth, spherical microparticles with good dispersibility. The cytotoxicity studies indicated greater anticancer activity for D6 (IC₅₀ = 4.85&#xa0;µg/mL) compared to pure AXT (IC₅₀ = 5.95&#xa0;µg/mL). The stability testing confirmed that drug integrity and aerosolization properties were retained over three months.</p> Conclusions <p>The optimized AXT spray-dried microparticles exhibited promising aerodynamic and biological properties, suggesting their suitability for pulmonary delivery. This formulation strategy offers a promising alternative to systemic administration, potentially improving local drug concentration in the lungs while limiting systemic toxicity in lung cancer therapy.</p> Graphical Abstract <p></p>

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Spray-Dried Inhalable Microparticles of Axitinib for the Treatment of Lung Cancer

  • 期刊论文

  • 发表日期：

    2025年11月25日

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  • Mahesh Nikhade,
  • Sachin S. Gaikwad,
  • Tejas Rangbhal,
  • Sujit A. Jadhav,
  • Himanshu Paliwal

摘要

Purpose

This research aims to develop a pulmonary delivery system of axitinib (AXT) as a spray-dried microparticle to address its poor solubility, variable oral bioavailability, and systemic adverse effects, thereby enhancing its potential application in LC therapy.

Methods

The microparticles were produced via spray drying using lactose and L-leucine as stabilizing carriers. The spray drying was carried out at an inlet/outlet temperature of 105 °C/60 °C, and feed rate of 2 mL/min. The formulations were characterized for production yield, drug content, solid-state analysis using DSC, PXRD, FTIR, morphology by SEM, aerosolization efficiency, and in vitro cytotoxicity activity against A549 lung carcinoma cells. Further, the stability of the optimized formulation was examined under accelerated conditions at 40 °C ± 2 °C and 75% ± 5% RH.

Results

Among the prepared formulations, the D6 formulation (84.56% of lactose, and 14.71% of L-leucine) demonstrated the most desirable performance, showing a high emitted dose (98.42%) and fine particle fraction (44.33%) with an MMAD of 2.11 μm. The solid-state studies confirmed the transformation of AXT into an amorphous form, improving the solubility of AXT. SEM images revealed smooth, spherical microparticles with good dispersibility. The cytotoxicity studies indicated greater anticancer activity for D6 (IC₅₀ = 4.85 µg/mL) compared to pure AXT (IC₅₀ = 5.95 µg/mL). The stability testing confirmed that drug integrity and aerosolization properties were retained over three months.

Conclusions

The optimized AXT spray-dried microparticles exhibited promising aerodynamic and biological properties, suggesting their suitability for pulmonary delivery. This formulation strategy offers a promising alternative to systemic administration, potentially improving local drug concentration in the lungs while limiting systemic toxicity in lung cancer therapy.

Graphical Abstract