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<p>Simvastatin (SMV), a repurposed drug, shows significant promise in lung cancer therapy. This study developed a promising inhalable microparticles of simvastatin-loaded nanostructured lipid carriers (SMV-NLC-MP) for pulmonary delivery. NLCs were prepared using biocompatible components, essential for long-term use and sustainability. The developed microparticles showed desirable physicochemical characteristics. SEM confirmed spherical morphology, while XRD revealed the amorphous nature of SMV. Aerosolization studies using a custom device showed efficient dose delivery (87%). Cytotoxicity against A549 cells showed superior anticancer activity for SMV-NLC-MP (IC<sub>50</sub> = 13.66 ± 0.20&#xa0;µg/mL) compared with SMV suspension (IC<sub>50</sub> = 30.26 ± 0.14&#xa0;µg/mL). In vivo pharmacokinetics in rats indicated C<sub>max</sub> of 37.08 ng/ml and AUC₀–₂₄ of 325.3 ng·h/mL for SMV-NLC-MP. Biodistribution confirmed preferential pulmonary accumulation (39.12 ± 2.4&#xa0;µg) with reduced off-target deposition. Pharmacodynamic studies demonstrated significant tumor volume reduction (82.4 ± 7.8&#xa0;mm³), normalization of lung weight, and maximum tumor inhibition (66.37 ± 1.2%). Histology verified preserved lung architecture and biocompatibility. Six-month stability studies revealed non-significant changes in the physicochemical parameters. This platform shall be sustainable in terms of low cost, less toxicity, environment friendly, and high patient compliance. This study demonstrates strong clinical translational potential as a novel inhalable therapy for lung cancer management.</p>

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Inhalable Microparticles of Simvastatin-Loaded Nanostructured Lipid Carriers for Lung Cancer Treatment: Drug Delivery Development, In Vitro Characterization, and In Vivo Evaluation

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Nargis Ara,
  • Abdul Hafeez,
  • Shom Prakash Kushwaha,
  • Archita Kapoor

摘要

Simvastatin (SMV), a repurposed drug, shows significant promise in lung cancer therapy. This study developed a promising inhalable microparticles of simvastatin-loaded nanostructured lipid carriers (SMV-NLC-MP) for pulmonary delivery. NLCs were prepared using biocompatible components, essential for long-term use and sustainability. The developed microparticles showed desirable physicochemical characteristics. SEM confirmed spherical morphology, while XRD revealed the amorphous nature of SMV. Aerosolization studies using a custom device showed efficient dose delivery (87%). Cytotoxicity against A549 cells showed superior anticancer activity for SMV-NLC-MP (IC50 = 13.66 ± 0.20 µg/mL) compared with SMV suspension (IC50 = 30.26 ± 0.14 µg/mL). In vivo pharmacokinetics in rats indicated Cmax of 37.08 ng/ml and AUC₀–₂₄ of 325.3 ng·h/mL for SMV-NLC-MP. Biodistribution confirmed preferential pulmonary accumulation (39.12 ± 2.4 µg) with reduced off-target deposition. Pharmacodynamic studies demonstrated significant tumor volume reduction (82.4 ± 7.8 mm³), normalization of lung weight, and maximum tumor inhibition (66.37 ± 1.2%). Histology verified preserved lung architecture and biocompatibility. Six-month stability studies revealed non-significant changes in the physicochemical parameters. This platform shall be sustainable in terms of low cost, less toxicity, environment friendly, and high patient compliance. This study demonstrates strong clinical translational potential as a novel inhalable therapy for lung cancer management.