Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons

Gagnadoux, Frédéric; Leblond, Valérie; Vecellio, Laurent; Hureaux, J.; Pape, Alain Le; Boisdron‐Celle, Michèle; Montharu, J.; Majoral, Caroline; Fournier, J.; Urban, T.; Diot, Patrice; Racineux, Jean-Louis; Lemarié, É.

doi:10.1007/s00280-005-0146-9

Cited by 26 publications

(20 citation statements)

References 16 publications

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“…Clinical and toxicological studies have been performed by drug aerosolization using this solution for injection in mice, rats, dogs, and baboons. (70)(71)(72)(73)(74) The most important features of these studies can be seen in Table 3.…”

Section: Methotrexatementioning

confidence: 99%

Formulations for Pulmonary Administration of Anticancer Agents to Treat Lung Malignancies

Carvalho

McConville

2011

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Chemotherapy plays a significant role both as primary and as supportive care for lung cancer treatment. The majority of currently available anticancer agents are administrated intravenously, causing side effects due to the systemic drug distribution. Alternatively, the bioavailability of orally administrated anticancer agents is usually compromised by the first-pass metabolism. Pulmonary administration may be a potential route for anticancer drug delivery to treat lung tumors, due to its site specific delivery, avoidance of first-pass metabolism, possibility of fewer side effects, and improved comfort for cancer patients using a needle-free delivery device. However, to attain an effective inhalational delivery, there is a requirement to design a formulation with appropriate aerodynamic properties with well-suited excipients. This review article explores work to date related to the formulations developed for pulmonary delivery of small molecule antineoplastic agents to treat primary and metastatic lung carcinomas. Ultimately, it highlights the importance of formulation design to define the role of inhalational chemotherapy.

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Section: Methotrexatementioning

confidence: 99%

Formulations for Pulmonary Administration of Anticancer Agents to Treat Lung Malignancies

Carvalho

McConville

2011

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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“…Recently, Gagnadoux et al (2005) demonstrated that gemcitabine (GEM) could be administered via endotracheal spray in rats without any marked toxicity at a maximum tolerated dose of 4-6 mg/kg body weight once a week for 9 consecutive weeks. Jet nebulization does not alter the cytotoxic properties of GEM (Gagnadoux et al 2006). Koshkina and Kleinerman (2005) demonstrated that GEM administered via aerosol inhibited the growth of lung metastasis in two osteosarcoma lung metastasis animal models.…”

Section: Introductionmentioning

confidence: 98%

Gemcitabine-loaded chitosan microspheres. Characterization and biological in vitro evaluation

Ventura

Cannavà

Stancanelli

et al. 2011

Biomed Microdevices

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This study investigates the potential of chitosan microspheres as delivery systems for the anticancer drug gemcitabine. The microspheres were obtained by spray-drying chitosan-gemcitabine solutions containing different amounts of the polyanion dextran sulphate. Morphological characterization by SEM and FIB analyses showed the presence of porous spherical particles having sizes ranging from about 1 to 5 μm. Dextran sulphate improves the technological parameters of the systems by producing very high encapsulation efficiency (about 96%, w/w) and by influencing the in vitro release of gemcitabine. The immediate drug release observed in the system prepared without dextrane sulphate (complete drug release within 30 min) was somewhat reduced by the polyanion (immediate release of 70% (w/w) of the encapsulated drug within 30 min, and subsequent continued release of the remaining 30% of the drug for over 4 days). The anti-tumoral efficacy of the various formulations was tested in vitro on human lung cancer cells (A549) comparing the effects with those of the free drug or drug/dextran sulfate complex. The carriers improved the cytotoxic activity of the drug, particularly the formulation containing the lowest amount of dextran sulphate after 72 h incubation.

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“…A study by Gagnadoux et al showed that the cytotoxicity of a nebulised formulation of the nucleoside analog gemcitabine (GCB) was similar to that of the native drug when tested against NCI-H460 and A549 Non-Small Cell Lung Cancer (NSCLC) cells (Gagnadoux et al, 2006). Another study of the cytotoxicity of a nebulised farnesol formulation containing polysorbate 80 (Tween 80) in vitro for NSCLC lines (H460 and A549) showed that the anticancer properties of nebulised farnesol were essentially the same as those of the native drug (Wang et al, 2003).…”

Section: Pharmacological Properties Of Aerosolised Anticancer Agentsmentioning

confidence: 99%

“…injection (Selting et al, 2008). Gemcitabine was given to 3 baboons via the airways and its concentration in the blood was 25 times lower than after its systemic delivery (Gagnadoux et al, 2006). Dogs with spontaneous pulmonary metastases were given aerosolized paclitaxel and doxorubicin and the drug concentrations in the bloodstream were measured 1 minute later (Hershey et al, 1999).…”

Section: Blood Passagementioning

confidence: 99%

The Airways: A Promising Route for the Pulmonary Delivery of Anticancer Agents

Guilleminault¹,

Hervé-Grépinet²,

Lemarié³

et al. 2011

Advances in Cancer Therapy

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Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons

Cited by 26 publications

References 16 publications

Formulations for Pulmonary Administration of Anticancer Agents to Treat Lung Malignancies

Formulations for Pulmonary Administration of Anticancer Agents to Treat Lung Malignancies

Gemcitabine-loaded chitosan microspheres. Characterization and biological in vitro evaluation

The Airways: A Promising Route for the Pulmonary Delivery of Anticancer Agents

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