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

Elkady, Omar A; Saleh, Layla M.; Tadros, Mina Ibrahim; El-Laithy, Hanan M.

doi:10.1208/s12249-021-02078-8

Cited by 3 publications

(2 citation statements)

References 48 publications

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“…The suppression of inflammatory cells’ accumulation, especially macrophages’ infiltration was observed in COPD rats treated with RIS. The macrophages’ apoptosis induced by bisphosphonates was reported as one mechanism of ameliorating emphysema [ 12 , 36 ]. In our study, the bronchodilatation was monitored immediately and obviously in COPD animals after RIS administration, and the detection time was relatively short.…”

Section: Discussionmentioning

confidence: 99%

Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling

Liu

Tang

et al. 2022

Respir Res

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Background Chronic obstructive pulmonary disease (COPD) is a progressive disorder that causes airway obstruction and lung inflammation. The first-line treatment of COPD is the bronchodilators of β2-agonists and antimuscarinic drugs, which can help control the airway obstruction, but the long-term use might render the drug tolerance. Bisphosphonates are widely used in osteoclast-mediated bone diseases treatment for decades. For drug repurposing, can delivery of a third generation of nitrogen-containing bisphosphonate, risedronate (RIS) ameliorate the progression of COPD? Methods COPD rats or mice models have been established through cigarette-smoking and elastase injection, and then the animals are received RIS treatment via nebulization. Lung deposition of RIS was primarily assessed by high-performance liquid chromatography (HPLC). The respiratory parameters of airway obstruction in COPD rats and mice were documented using plethysmography method and resistance-compliance system. Results High lung deposition and bioavailability of RIS was monitored with 88.8% of RIS input dose. We found that RIS could rescue the lung function decline of airspace enlargement and mean linear intercept in the COPD lung. RIS could curb the airway obstruction by suppressing 60% of the respiratory resistance and elevating the airway’s dynamic compliance, tidal volume and mid-expiratory flow. As an inhibitor of farnesyl diphosphate synthase (FDPS), RIS suppresses FDPS-mediated RAS and RhoA prenylation to obstruct its membrane localization in airway smooth muscle cells (ASMCs), leading to the inhibition of downstream ERK-MLCK and ROCK1-MLCP pathway to cause ASMCs relaxation. Additionally, RIS nebulization impeded pro-inflammatory cell accumulation, particularly macrophages infiltration in alveolar parenchyma. The NF-κB, tumor necrosis factor-alpha, IL-1β, IL-8, and IL-6 declined in microphages following RIS nebulization. Surprisingly, nebulization of RIS could overcome the tolerance of β2-agonists in COPD-rats by increasing the expression of β2 receptors. Conclusions Nebulization of RIS could alleviate airway obstruction and lung inflammation in COPD, providing a novel strategy for treating COPD patients, even those with β2-agonists tolerance.

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Section: Discussionmentioning

confidence: 99%

Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling

Liu

Tang

et al. 2022

Respir Res

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“…Nanotechnology and nanocarriers have gained popularity delivering therapeutically active compounds into the lungs, offering a multitude of benefits, including; high drug loading, drug shielding from degradation, controlled drug release and biocompatibility, as well as stability of formulations during the nebulization process. Several lipid-based formulations have successfully delivered therapeutically active ingredients offering the aforementioned benefits into the pulmonary system, examples include; transfersomes and protransfersomes [5][6][7][8], niosomes and proniosomes [9,10], micelles [11], microspheres [12,13], solid lipid nanoparticles [14] and nanostructured lipid carriers [3,15].…”

Section: Introductionmentioning

confidence: 99%

Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor

Khan

Al-Hasani²,

Khan³

et al. 2023

PLoS ONE

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Drug delivery via aerosolization for localized and systemic effect is a non-invasive approach to achieving pulmonary targeting. The aim of this study was to prepare spray-dried proliposome (SDP) powder formulations to produce carrier particles for superior aerosolization performance, assessed via a next generation impactor (NGI) in combination with a dry powder inhaler. SDP powder formulations (F1-F10) were prepared using a spray dryer, employing five different types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) and two different dispersion media. The first dispersion medium was comprised of water and ethanol (50:50% v/v ratio), and the second dispersion medium comprised wholly of ethanol (100%). In the first dispersion medium, the lipid phase (consisting of Soya phosphatidylcholine (SPC as phospholipid) and Beclomethasone dipropionate (BDP; model drug) were dissolved in ethanol and the lactose carrier in water, followed by spray drying. Whereas in second dispersion medium, the lipid phase and lactose carrier were dispersed in ethanol only, post spray drying. SDP powder formulations (F1-F5) possessed significantly smaller particles (2.89 ± 1.24–4.48 ± 1.20 μm), when compared to SDP F6-F10 formulations (10.63 ± 3.71–19.27 ± 4.98 μm), irrespective of lactose carrier type via SEM (scanning electron microscopy). Crystallinity of the F6-F10 and amorphicity of F1-F15 formulations were confirmed by XRD (X-ray diffraction). Differences in size and crystallinity were further reflected in production yield, where significantly higher production yield was obtained for F1-F5 (74.87 ± 4.28–87.32 ± 2.42%) then F6-F10 formulations (40.08 ± 5.714–54.98 ± 5.82%), irrespective of carrier type. Negligible differences were noted in terms of entrapment efficiency, when comparing F1-F5 SDP formulations (94.67 ± 8.41–96.35 ± 7.93) to F6-F10 formulations (78.16 ± 9.35–82.95 ± 9.62). Moreover, formulations F1-F5 demonstrated significantly higher fine particle fraction (FPF), fine particle dose (FPD) and respirable fraction (RF) (on average of 30.35%, 890.12 μg and 85.90%) when compared to counterpart SDP powder formulations (F6-F10). This study has demonstrated that when a combination of water and ethanol was employed as dispersion medium (formulations F1-F5), superior formulation properties for pulmonary drug delivery were observed, irrespective of carrier type employed.

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Recent advancements and application of in vitro models for predicting inhalation toxicity in humans

Bedford¹,

Perkins²,

Clements³

et al. 2022

Toxicology in Vitro

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

Cited by 3 publications

References 48 publications

Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling

Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling

Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor

Recent advancements and application of in vitro models for predicting inhalation toxicity in humans

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