Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment

Almurshedi, Alanood S.; Aljunaidel, Hessah A; AlQuadeib, Bushra T.; Aldosari, Basmah N.; Alfagih, Iman M.; Almarshidy, Salma S; Eltahir, Eram; Mohamoud, Amany Z

doi:10.2147/ijn.s286896

Cited by 18 publications

(5 citation statements)

References 71 publications

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“…The greater FPF, smaller MMAD, and GSD imply stronger lung deposition, optimal aerosol particle size, and narrower particle size dispersion of the aerosol droplets. MMAD of 1−5 µm is considered ideal for delivery to deep lungs with minimum oropharynx deposition [44]. The results suggest that liposomal naringin possesses good aerosolization properties and is suitable for deep lung tissue drug delivery.…”

Section: In Vitro Lung Depositionmentioning

confidence: 98%

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

et al. 2021

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Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.

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Section: In Vitro Lung Depositionmentioning

confidence: 98%

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

et al. 2021

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“…Their study showed a remarkable improvement in the fine particle fraction (FPF) with enhancing lipid: chitosan proportions. Their findings concluded that novel inhalable CFX-loaded nanocomposite microparticle powders are a promising new strategy to ameliorate target potentiality and administration of CFX for bronchiectasis therapy [99]. In addition, Hisham and colleagues fabricated inhaled hybrid silver/CFX nanoparticles with synergistic effectiveness against P. aeruginosa.…”

Section: Cfx Inhalable Formulations For Lrtis Management In Preclinic...mentioning

confidence: 99%

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives

Panthi,

Fairfull-Smith,

Islam

2024

Pharmaceutics

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Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

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“…We investigated the powderological properties of the cepharanthine dry powder inhaler by measuring the bulk density and vibrational density of the powder (Table 3) and calculating its aerodynamic diameter (Da) according to the formula. The aerodynamic diameter is the most important factor affecting the deposition site of drugs, and it is generally considered that particles with Da within 1-5 μm can reach the deep lung [25]. Based on the Chinese Pharmacopoeia 2020 version of the "Inhalation preparation of fine particles, aerodynamic characteristics of the method" (General 0951)", Device 3" (Next generation cascade impactor, NGI) was used to examine the fine particle fraction (FPF) of this product to simulate the distribution of CEP dry powder inhaler in the lungs in vitro (Figure 4).…”

Section: Fine Particle Fractions and Powderological Investigation Of Cepmentioning

confidence: 99%

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Liang¹,

Wang²,

Chen³

et al. 2023

Molecules

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Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

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Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment

Cited by 18 publications

References 71 publications

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

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