FFC#19/2015

Inhalable formulations of new molecules effective against Burkholderia cenocepacia: from in vitro to in vivo applications

FFC#19/2015

Inhalable formulations of new molecules effective against Burkholderia cenocepacia: from in vitro to in vivo applications

PRINCIPAL INVESTIGATOR

Giovanna Riccardi (Laboratorio di Microbiologia Molecolare, Dipartimento di Biologia e Biotecnologie Lazzaro Spallanzani, Pavia)

Partner

Francesca Ungaro (Dip. di Farmacia – Università degli Studi Federico II, Napoli)

RESEARCHERS

11

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

2 years

GOAL

€ 60.000 €

RESULTS

Researchers focused their study on a benzothiadiazole derivative called C109. The characterization of the new molecule target has been pursued through biochemical experiments. Drug nanosuspensions were produced by evaporative precipitation into aqueous solution in the presence of different stabilizers and freeze-dried with a cryo-protectant. The resulting dry powder has been tested in vitro through the microdilution method, while cytotoxicity was checked through a cell viability assay. Meanwhile, in vivo toxicity and efficacy studies have been performed in healthy mice and in a mouse model of B. cenocepacia infection.
Inhalable formulations of C109 were developed, fully characterized in view of pulmonary delivery and tested against B. cenocepacia and CF human epithelial cells with good results. Nevertheless, in vivo experiments suggested a dose-dependent toxicity of the formulation when intratracheally administered in mice. To elucidate this phenomenon, C109 nanocrystals stabilised with different types and amounts of excipients are under investigation in vitro and in vivo.

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