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Aerodynamical, Immunological and Pharmacological Properties of the Anticancer Antibody Cetuximab Following Nebulization

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Abstract

Purpose

Despite an increasing interest in the use of inhalation for local delivery of molecules for respiratory diseases and systemic disorders, methods to deliver therapy through airways has received little attention for lung cancer treatment. However, inhalation of anticancer drugs is an attractive alternative route to systemic administration which results in limited concentration of the medication in the lungs, and triggers whole-body toxicity. In this study, we investigated the feasibility of nebulization for therapeutic antibodies, a new class of fully-approved anticancer drugs in oncology medicine.

Materials and methods

Cetuximab, a chimeric IgG1 targeting the epidermal growth factor receptor (EGFR), was nebulized using three types of delivery devices: a jet nebulizer PARI LC+®, a mesh nebulizer AeronebPro® and an ultrasonic nebulizer SYST’AM® LS290. Aerosol size distribution was measured using a cascade impactor and aerosol droplets were observed under optical microscopy. The immunological and pharmacological properties of cetuximab were evaluated following nebulization using A431 cells.

Results

The aerosol particle clouds generated with the three nebulizers displayed similar aerodynamical characteristics, but the IgG formed aggregates in liquid phase following nebulization with both the jet and ultrasonic devices. Flow cytometry analyses and assays of EGFR-phosphorylation and cell growth inhibitions on A431 demonstrated that both the mesh and the jet nebulizers preserved the binding affinity to EGFR and the inhibitory activities of cetuximab.

Conclusions

Altogether, our results indicate that cetuximab resists the physical constraints of nebulization. Thus, airway delivery represents a promising alternative to systemic administration for local delivery of therapeutic antibodies in lung cancer treatment.

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Acknowledgements

We thank Michèle De Monte for helpful suggestions in statistical analysis. This work was supported by grants from Cancéropôle Grand Ouest, IFR135 (Institut Fédératif de Recherche), la Ligue contre le Cancer. Agnès Maillet’s fellowships were donated by SPLF (Société de Pneumologie de Langue Française) and Pneumologie Dévelopement.

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Authors and Affiliations

  1. U618, Protéases et vectorisation Pulmonaires, Université François-Rabelais de Tours, Tours, France

    Agnès Maillet, Laurent Vecellio, Sophie Hamard, Yves Courty, Francis Gauthier, Patrice Diot, Etienne Lemarié & Nathalie Heuzé-Vourc’h

  2. UPRES EA 3853, Immuno-Pharmaco-Génétique des Anticorps thérapeutiques (IPGA), Université François-Rabelais de Tours, Tours, France

    Nicolas Congy-Jolivet & Gilles Thibault

  3. CHRU de Tours, 37000, Tours, France

    Nicolas Congy-Jolivet, Patrice Diot, Gilles Thibault & Etienne Lemarié

  4. Atomisor, DTF, 42003, Saint Etienne, France

    Sandrine Le Guellec

  5. Laboratoire de Thérapie Cellulaire et Immunobiologie du Cancer, CHU Morvan de Brest, Université de Bretagne Occidentale, Brest, France

    Anthony Courtois

  6. Laboratoire de Biotechnologie et Molécules marines, IFREMER, Plouzané, France

    Anthony Courtois

  7. INSERM U618—Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours cedex 1, France

    Nathalie Heuzé-Vourc’h

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  1. Agnès Maillet
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  2. Nicolas Congy-Jolivet
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  3. Sandrine Le Guellec
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Correspondence to Nathalie Heuzé-Vourc’h.

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Maillet, A., Congy-Jolivet, N., Le Guellec, S. et al. Aerodynamical, Immunological and Pharmacological Properties of the Anticancer Antibody Cetuximab Following Nebulization. Pharm Res 25, 1318–1326 (2008). https://doi.org/10.1007/s11095-007-9481-3

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  • DOI: https://doi.org/10.1007/s11095-007-9481-3

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