Inhaled Chemotherapy in Lung Cancer: Safety Concerns of Nanocomplexes Delivered

Zarogoulidis, Paul; Gialeli, Chrysostomi; Karamanos, Nikos K.

doi:10.4155/tde.12.77

Cited by 34 publications

(29 citation statements)

References 23 publications

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“…For instance, (liposomal) amphotericin B [54] for the treatment of fungal infections has already been tested as dry powder. Also particularly interesting for inhalation as a dry powder are chemotherapeutics in lung cancer [55,56], drugs preventing rejection after a lung transplantation, like cyclosporine A [57,58] or drugs for the treatment of pulmonary arterial hypertension [59].…”

Section: Miscellaneous For Local Actionmentioning

confidence: 99%

The role of disposable inhalers in pulmonary drug delivery

Boer¹,

Hagedoorn²

2014

Expert Opinion on Drug Delivery

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Prerequisites for the use of disposable inhalers, particularly dry powder inhalers, in applications such as childhood vaccination and for preventing or stopping pandemic outbreaks of highly infectious diseases (like influenza, bird flu, SARS) are that they are simple, cheap and effective. Not only do the devices have to be simple in design, but the drug formulations should also be cheap. This may require a different approach as the formulation may not need to be adapted to improve the inhaler must be designed to enhance formulation dispersion.

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Section: Miscellaneous For Local Actionmentioning

confidence: 99%

The role of disposable inhalers in pulmonary drug delivery

Boer¹,

Hagedoorn²

2014

Expert Opinion on Drug Delivery

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“…However; the safety issue still remains since adverse effects such as non-specific inflammation of the airways or pulmonary edema was observed at least for gemcitabine and paclitaxel [24]. We should take under consideration that the formulations administered were not designed for the airways therefore possibly novel compounds should be considered [26,27]. Moreover; all trials were performed either in patients with advanced stage disease or as a short term animal experiments, therefore the safety matter was not properly assessed since an extended time of observation at least more than 6 months is necessary.…”

Section: Lung Cancer Treatmentmentioning

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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“…Moreover, safety issue remains a major consideration for inhaled chemotherapeutics. The inhalation of cytotoxic drugs may cause transient high local drug concentrations, which may lead to toxicity to the lung tissue [7][8][9]. Therefore, the benefits and the challenges of inhaled chemotherapy have stimulated interests in the development of delivery systems for retaining and progressively releasing anti-cancer drugs in the lungs [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

Luo

Loira-Pastoriza

Patil

et al. 2016

Journal of Controlled Release

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The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. AbstractPulmonary delivery offers an attractive route of administration for chemotherapeutic agents, with the advantages of high drug concentrations locally and low side effects systemically. However, fast clearance mechanisms result in short residence time of small molecule drugs in the lungs. Moreover, the local toxicity induced by antineoplastic drugs is considered a major obstacle for the clinical application of inhaled chemotherapy. In this study, we explored the utility of 6 kDa and 20 kDa polyethylene glycol-paclitaxel (PEG-PTX) conjugates to retain paclitaxel within the lungs, achieve its sustained release locally, and thereby, improve its efficacy and reduce its pulmonary toxicity. The conjugates increased the maximum tolerated dose of paclitaxel by up to 100-fold following intratracheal instillation in healthy mice. PEG-PTX conjugates induced lung inflammation. However, the inflammation was lower than that induced by an equivalent dose of the free drug and it was reversible. Conjugation of paclitaxel to both PEG sizes significantly enhanced its anti-tumor efficacy following intratracheal instillation of a single dose in a Lewis lung carcinoma model in mice. PEG-PTX 20k showed equivalent efficacy as PEG-PTX 6k delivered at a 2.5-fold higher dose, suggesting that the molecular weight of the conjugate plays a role in anti-cancer activity. PEG-PTX 20k conjugate presented a prolonged residency and a sustained paclitaxel release within the lungs. This study showed that PEGylation of paclitaxel offers a potential delivery system for inhalation with improved anti-cancer efficacy, prolonged exposure of lung-resident tumors to the antineoplastic drug and reduced local toxicity.

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Inhaled Chemotherapy in Lung Cancer: Safety Concerns of Nanocomplexes Delivered

Cited by 34 publications

References 23 publications

The role of disposable inhalers in pulmonary drug delivery

The role of disposable inhalers in pulmonary drug delivery

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

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

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