FN Archimer Export Format PT J TI Aerodynamical, immunological and pharmacological properties of the anticancer antibody cetuximab BT AF MAILLET, A CONGY JOLIVET, N LE GUELLEC, S VECELLIO, L HAMARD, S COURTY, Y COURTOIS, Anthony GAUTHIER, F DIOT, P THIBAULT, G LEMARIE, E HEUZE VOURC' H, N AS 1:1;2:2,3;3:4;4:1;5:1;6:1;7:5,6;8:1;9:1,3;10:2,3;11:1,3;12:1,7; FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:;12:; C1 Univ Tours, U618, Tours, France. Univ Tours, UPRES EA 3853, IPGA, Tours, France. CHRU Tours, F-37000 Tours, France. DTF, Atomisor, F-42003 St Etienne, France. Univ Bretagne Occidentale, Lab Therapie Cellulaire & Immunobiol Canc, CHU Morvan Brest, Brest, France. IFREMER, Lab Biotechnol & Mol Marines, Plouzane, France. Fac Med, INSERM, U618, F-37032 Tours, France. C2 UNIV TOURS, FRANCE UNIV TOURS, FRANCE CHRU TOURS, FRANCE DTF, FRANCE UBO, FRANCE IFREMER, FRANCE UNIV TOURS, FRANCE SI BREST SE PDG-DOP-DCB-BM-BMM IN WOS Ifremer jusqu'en 2018 copubli-france copubli-univ-france IF 4.024 TC 39 UR https://archimer.ifremer.fr/doc/2008/publication-4201.pdf LA English DT Article DE ;Nebulizer;Lung cancer;Cetuximab;Anticancer antibody;Aggregation;Aerosol AB 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 air-ways 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 (EGER), was nebulized using three types of delivery devices: a jet nebulizer PARI LC+(R), a mesh nebulizer AeronebPro (R) and an ultrasonic nebulizer SYST'AM (R) 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 EGER 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. PY 2008 PD JUL SO Pharmaceutical Research SN 0724-8741 PU Springer VL 25 IS 6 UT 000255753900007 BP 1318 EP 1326 DI 10.1007/s11095-007-9481-3 ID 4201 ER EF