Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease

Ibrahim, Basma M.; Tsifansky, Michael D.; Yang, Yan; Yeo, Yoon

doi:10.1517/17425247.2011.561310

Cited by 31 publications

(55 citation statements)

References 191 publications

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“…Furthermore, another study successfully demonstrates the gene delivery with magnetized aerosol comprising iron oxide nanoparticles in lungs of mice [43]. Therefore, administration of drugs via the inhalation route is of great interest in CF treatment [44]. The main advantages of aerosol technologies are the limited systemic toxicity, direct drug action on target site and the suitability for home therapy [45].…”

Section: Different Delivery Methodsmentioning

confidence: 99%

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

et al. 2016

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Background: Cystic fibrosis (CF) is the most common life-threatening inherited disease in the Caucasian population. It is caused by genetic defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR), a cAMP regulated chloride-bicarbonate channel mainly located in the apical membrane of polarized epithelial cells. CFTR is proposed to regulate other proteins, including the epithelial sodium channel (ENaC). Recently, we successfully restored chloride current in CFTR deficient human airway epithelial cells using wtCFTR-mRNA transfection compared to non-CF cells showing similar values. The present study aimed to optimize the wtCFTR-mRNA transfection procedures in primary cultured human nasal epithelial (HNE) cells. Methods: Dose and time dependence experiments were performed. In addition, we investigated the possible impact of the wtCFTR-mRNA transfection on ENaC function in transepithelial measurements. We reduced the wtCFTR-mRNA dose stepwise and determined the minimal concentration of 0.6 μg/cm

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Section: Different Delivery Methodsmentioning

confidence: 99%

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

et al. 2016

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“…Antibiotics delivered for treating bacterial infections associated with these diseases needs to penetrate the sputum and distribute evenly. Drugs such as ion-channel modulators or gene therapeutics which need to reach the epithelial layer must first traverse the thick mucus layer to achieve their desired activity [100,101].…”

Section: Sputummentioning

confidence: 99%

“…The increased presence of mucin glycoproteins in the sputum of patients immobilizes P. aeruginosa by surface interactions, which has increased tolerance to antibiotics resisting clearance from these hypoxic mucopurulent masses in the airway [98,105]. The CF sputum is the reason for failure of drug delivery and hence treatment [100,101]. Moreover, antibodies and fragments along with other soluble factors act as molecular traps for viral gene delivery, as demonstrated for adenoviral gene delivery due to the presence of adenoviral antibodies [100].…”

Section: Sputummentioning

confidence: 99%

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A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

Merchant

Buckton²,

Taylor³

et al. 2016

CPD

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Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilmassociated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance.

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“…Moreover, systemic exposure is reduced, decreasing the potential systemic side effects or drug-drug interactions. Therefore, inhalation has become the preferential route of administration to treat respiratory disorders such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, and is in development for other pulmonary disorders [18,[20][21][22][23][24]. The effectiveness of treatment by the pulmonary route depends mainly on the deposition of drug-based particles and therefore on their aerodynamic diameters (d ae ).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Recent Developments in Inhaled Triazoles Against Invasive Pulmonary Aspergillosis

Merlos

Amighi

Wauthoz

2014

Curr Fungal Infect Rep

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Invasive pulmonary aspergillosis (IPA) presents high incidence and high mortality in immunocompromised patients. To combat or prevent IPA, triazoles such as voriconazole or itraconazole and posaconazole are becoming the first-or second-line therapy, respectively.However, triazoles present issues of oral bioavailability, high liver metabolism and/or drugdrug interactions, increasing the variability of systemic concentrations. To overcome these issues, inhalation is a promising route for delivering triazoles for prophylactic or curative therapy of IPA. Indeed, pulmonary drug delivery increases the drug in situ drastically while decreasing the systemic exposure, therefore limiting drug metabolisation, side effects and drug-drug interactions. Development of triazoles for inhalation has focused on voriconazole and itraconazole, drugs which are both highly permeable but present high solubility differences. In this review, the most complete and promising pharmaceutical developments for voriconazole and itraconazole are described.Keywords: aerosol, antifungal, aspergillosis, fungal infection, pulmonary delivery, dry powder inhaler, dry powder for inhalation, nebulizer, nebulization, cyclodextrin, nanoparticle, solid dispersion, controlled release drug delivery. Abbreviations: AI90H, amorphous itraconazole with Phospholipon

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Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease

Abstract: An ideal drug/gene delivery system to CF airways should overcome the tenacious sputum, which presents physical, chemical and biological barriers to effective transport of therapeutic agents to the targets and various cellular challenges.

Cited by 31 publications

References 191 publications

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

Recent Developments in Inhaled Triazoles Against Invasive Pulmonary Aspergillosis

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