Defense Mechanisms of the Respiratory System and Aerosol Production Systems

Darwiche, Kaid; Yarmus, Lonny; Spyratos, Dionysios; Sečen, Nevena; Hohenforst-Schmidt, Wolfgang; Katsikogiannis, Nikolaos; Huang, Haidong; Gschwendtner, Andreas; Zarogoulidis, Konstantinos

doi:10.2174/157340641130900041

Cited by 14 publications

(14 citation statements)

References 92 publications

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“…The respiratory system has defense mechanisms which protect the epithelium against bacterial infection and foreign particles/molecules from being deposited 29. These mechanisms can be summarized to the following: a) beating cilia, b) mucus, c) macrophages, d) transporters and e) enzymes.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

Hohenforst-Schmidt¹,

Linsmeier²,

Kioumis³

et al. 2014

J. Cancer

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Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs® in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes.

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Section: Discussionmentioning

confidence: 99%

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

Hohenforst-Schmidt¹,

Linsmeier²,

Kioumis³

et al. 2014

J. Cancer

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“…Time-consuming aerosol administration can cause adverse effects, such as cough 8. Finally, cup design D is suggested as the most effective cup for lowering the droplet size (2.30 μm) when considering a higher loading level (8 mL).…”

Section: Discussionmentioning

confidence: 99%

“…Several drugs for systemic diseases are currently being investigated for aerosol administration 1–7. The respiratory system has several defense mechanisms that the aerosol droplets or dry powder have to bypass in order to deposit in the alveoli 8. The beating cilia, mucus, and macrophages are the most important obstacles.…”

Section: Introductionmentioning

confidence: 99%

Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

Kioumis¹,

Lampaki²,

Organtzis³

et al. 2014

DDDT

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BackgroundAt this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases.Materials and methodsThe drugs linezolid (Zyvox), vancomycin (Voncon), and daptomycin (Cubicin) were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments.ResultsWhen drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 μm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 μm) when considering a higher loading level (8 mL).ConclusionModification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the nebulization systems have the same properties.

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“…Local factors of the airways such as the macrophages, transporters or local gene expression play a role in the absorption of the drug and these are parameters that can be modified. The patient target group should be considered as some devices need synchronization upon device activation and patient inspiration [4,[10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Breathing patterns also modify the deposition of aerosol within the airways, and therefore correct usage of inhalable devices is necessary.…”

Section: Aerosol Administrationmentioning

confidence: 99%

“…The distribution and deposition is affected by the stage of the underlying disease and whether there is exacerbation when the drug is administered, the mass median aerodynamic diameter (mmad) of the particles (should be <5μm), local transporters and gene expression on the bronchial tree, humidity of the airways and solubility. These factors will be thoroughly explained in the Ivyspring International Publisher following sections [4]. In the current work we will present methods that can be easily used by clinical doctors in the laboratory in order to repurpose a drug from one form to another based on previous published work from our institutions.…”

Section: Introductionmentioning

confidence: 99%

Drug development of Lung Diseases by way of Drug Repurposing; What a Pulmonary Physician can do in the Laboratory

Tsiouda¹,

Hohenforst-Schmidt²,

Sardeli³

et al. 2018

J. Biomed

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Lung diseases are very common among several patients such as; asthma, chronic obstructive pulmonary disease, lung cancer, cystic fibrosis and pulmonary fibrosis. In many of these diseases we already have inhalation therapies, however; for others we have only systematic administration. There are also diseases of the lung that cause pulmonary hypertension and architectural damage to the lung such as; emphysema and bronchiectasis. Several of the drugs currently administered intravenously are being investigated whether they could be transformed and delivered as aerosol therapy. We will present the methodology that can be used and has been used for several drugs.

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Defense Mechanisms of the Respiratory System and Aerosol Production Systems

Cited by 14 publications

References 92 publications

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System

Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

Drug development of Lung Diseases by way of Drug Repurposing; What a Pulmonary Physician can do in the Laboratory

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