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Purpose <p>Pulmonary arterial hypertension (PAH) remains a life-threatening disorder requiring innovative therapies to overcome the limitations of conventional sildenafil (SDF) administration. This study aimed to develop and optimize inhalable SDF-loaded novasomes (SDF-NVS) for efficient pulmonary delivery.</p> Methods <p>Using a Box–Behnken design, the effects of stearic acid, cholesterol, and Span 60 concentrations were evaluated on vesicle size (VS), entrapment efficiency (EE%), and cumulative release (CR%).</p> Results <p>The optimized formulation exhibited nanosized vesicles (205.36&#xa0;nm), high EE% (73.16%), and sustained drug release (85.61% over 8&#xa0;h). Transmission electron microscopy confirmed the spherical morphology of the optimum formulation, while the stability studies over three months showed almost no alteration in the physicochemical properties. Histopathological evaluation of lung tissues showed no inflammation, indicating the safety of repeated intratracheal administration. During pharmacokinetic studies, it was found that SDF-NVS offered increased bioavailability when delivered intratracheally in comparison to oral and intratracheal administration of SDF suspension. The SDF-NVS formulation showed a Cmax and AUC<sub>0−∞</sub> that was 3.2 and 5.1-fold, respectively, greater than the oral suspension. Additionally, it increased the half-life of SDF to 11.52&#xa0;h, which in turn led to a relative bioavailability of 506%. </p> Conclusion <p>These results highlight the safety and efficacy of novasomes as a pulmonary nanoplatform for SDF, with improved bioavailability, sustained release, and enhanced therapeutic outcomes in the management of pulmonary arterial hypertension.</p> Graphical Abstract <p></p>

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Inhalable Sildenafil-Loaded Novasomes for Targeted Pulmonary Delivery in Pulmonary Arterial Hypertension: Formulation Optimization, Safety Evaluation, and Pharmacokinetic Assessment

  • 期刊论文

  • 发表日期：

    2026年3月4日

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  • Dhari K. Luhaibi,
  • Adel A. Ali,
  • Essam M. Eissa,
  • Mohammed H. Elkomy,
  • Hussein M. Eid

摘要

Purpose

Pulmonary arterial hypertension (PAH) remains a life-threatening disorder requiring innovative therapies to overcome the limitations of conventional sildenafil (SDF) administration. This study aimed to develop and optimize inhalable SDF-loaded novasomes (SDF-NVS) for efficient pulmonary delivery.

Methods

Using a Box–Behnken design, the effects of stearic acid, cholesterol, and Span 60 concentrations were evaluated on vesicle size (VS), entrapment efficiency (EE%), and cumulative release (CR%).

Results

The optimized formulation exhibited nanosized vesicles (205.36 nm), high EE% (73.16%), and sustained drug release (85.61% over 8 h). Transmission electron microscopy confirmed the spherical morphology of the optimum formulation, while the stability studies over three months showed almost no alteration in the physicochemical properties. Histopathological evaluation of lung tissues showed no inflammation, indicating the safety of repeated intratracheal administration. During pharmacokinetic studies, it was found that SDF-NVS offered increased bioavailability when delivered intratracheally in comparison to oral and intratracheal administration of SDF suspension. The SDF-NVS formulation showed a Cmax and AUC0−∞ that was 3.2 and 5.1-fold, respectively, greater than the oral suspension. Additionally, it increased the half-life of SDF to 11.52 h, which in turn led to a relative bioavailability of 506%.

Conclusion

These results highlight the safety and efficacy of novasomes as a pulmonary nanoplatform for SDF, with improved bioavailability, sustained release, and enhanced therapeutic outcomes in the management of pulmonary arterial hypertension.

Graphical Abstract