Aerodynamical, immunological and pharmacological properties of the anticancer antibody cetuximab following nebulization.
OBJECTIVE
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.


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.
Maillet
Agnès
A
U618, Protéases et vectorisation Pulmonaires, Université François-Rabelais de Tours, Tours, France.
Congy-Jolivet
Nicolas
N
Le Guellec
Sandrine
S
Vecellio
Laurent
L
Hamard
Sophie
S
Courty
Yves
Y
Courtois
Anthony
A
Gauthier
Francis
F
Diot
Patrice
P
Thibault
Gilles
G
Lemarié
Etienne
E
Heuzé-Vourc'h
Nathalie
N
D000336:Aerosols; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009330:Nebulizers and Vaporizers; D010766:Phosphorylation
D000336:Aerosols; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab