Evaluation of Lung Cell Toxicity of Surfactants for Inhalation Route

F Lindenberg (1, 2) , François Sichel (3, 1) , Mathilde Lechevrel (1) , R Respaud (4) , Guillaume Saint-Lorant (1, 2)

1 ABTE - Aliments Bioprocédés Toxicologie Environnements
2 Service de Pharmacie [CHU Caen]
3 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
4 CEPR - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100

Few data are available for excipients administered by inhalation route. This study evaluated the in vitro potential toxicity of three surfactants (Polysorbate 20, Polysorbate 80 and Poloxamer 188) by using an original air-liquid interface (ALI) method of exposure compared to liquid/liquid (L/L) model. Two cell toxicity tests were conducted on BEAS-2B cells, a human immortalized bronchial epithelial cell lines; measurement of Lactate Dehydrogenase activity and XTT cell proliferation assay. We found that Polysorbate 20 appeared to be more toxic than Polysorbate 80, Poloxamer 188. An increased toxicity of Polysorbate 20 in L/L system as shown in comparison to ALI exposure. A toxicity was also observed for polysorbate 80 but at higher concentrations and without difference between L/L and ALI exposure. No toxicity was observed for Poloxamer 188 at high concentrations. Poloxamer 188 seems to be the better candidate, out of the three tested, for galenic formulations designed to the inhalation route such as biotherapies. To evaluate the cytotoxicity of excipients for inhalation route the ALI exposure have to be used instead of L/L.

Keywords: Excipients; Surfactants; Toxicity; ALI exposure; Inhalation route

Domains: Life Sciences [q-bio]; Toxicology

F Lindenberg, François Sichel, Mathilde Lechevrel, R Respaud, Guillaume Saint-Lorant. Evaluation of Lung Cell Toxicity of Surfactants for Inhalation Route. Journal of Toxicology and Risk Assessment, 2019, 5 (1), pp.133. ⟨10.23937/2572-4061.1510022⟩. ⟨hal-02448735⟩