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Nebulization of Risedronate Sodium Microspheres for Potential Attenuation of Pulmonary Emphysema: a Promising New Insight of Alveolar Macrophage Apoptosis

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Abstract

Risedronate sodium (RS) is a potent nitrogen-containing bisphosphonate which is known to induce osteoclast apoptosis. As a drug repurposing approach, the current work explored the potential of nebulizable RS-chitosan (CS) microspheres to induce alveolar macrophage apoptosis. RS-CS microspheres were assessed for lung deposition, cytotoxicity, and cellular uptake percentage in Calu-3 cells. The potential of nebulizable microspheres for treating elastase-induced emphysema in rats was investigated, compared to RS marketed oral tablets®, with respect to histopathological, immunohistochemical, and flow cytometric studies. The in vitro lung deposition pattern suggested deep alveolar deposition of RS microspheres, with respect to high FPF% and suitable MMAD (66% and 1.506 μm, respectively, at a flow rate of 28.3 L min−1). No apparent cytotoxicity was observed, with a cell viability > 90%. The inhalation of RS-CS microspheres was suggested to inhibit airspace enlargement and lung rarefaction after elastase instillation and reduce the macrophage accumulation in alveolar parenchyma. Immunohistochemical and cytometric analyses revealed significant low expression levels of CD68 and CD11b surface markers, respectively, with significantly (P < 0.05) lower detected numbers of intact alveolar macrophages following inhalation of RS-CS microspheres. The nebulization of RS-CS microspheres could induce apoptosis in alveolar macrophages and be promisingly adopted for attenuation of pulmonary emphysema.

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Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt

    Omar A. Elkady & Hanan M. El-laithy

  2. Hematology section, Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Layla M. Saleh

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Mina Ibrahim Tadros & Hanan M. El-laithy

  4. Department of Pharmaceutics, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt

    Mina Ibrahim Tadros

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  1. Omar A. Elkady
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  4. Hanan M. El-laithy
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The authors contributed equally to this work and participated in the following:

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Correspondence to Mina Ibrahim Tadros.

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Elkady, O.A., Saleh, L.M., Tadros, M.I. et al. Nebulization of Risedronate Sodium Microspheres for Potential Attenuation of Pulmonary Emphysema: a Promising New Insight of Alveolar Macrophage Apoptosis. AAPS PharmSciTech 22, 202 (2021). https://doi.org/10.1208/s12249-021-02078-8

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