Patients suffering of chronic lung diseases, diabetes, autoimmune diseases, immunodeficencies are particularly at risk for opportunistic infections. Moreover, persistent inflammation usually plays an important role in exacerbating the underlying condition. Chronic inflammation in fact is a major cause of hospitalization that is responsible of high exposure to infection and represents a burden for financial health system. The identification of a convenient therapeutic approach, able to simultaneously target both infection and inflammation, would be highly desirable the medical community.
The objective of the present project is to exploit the modulation of sphingolipid molecules as new therapeutic targets in pulmonary inflammation and infections. Due to the lipophilic nature of sphingolipid metabolism inhibitors, drug delivery will be obtained via novel and promising nanocarriers and results will be validated
in vitro
and
in vivo
.
The main objectives of the present project are: i) to study the antimicrobial activity of sphingolipid metabolism inhibitors (SMIs) at the aim of proposing a new therapeutic role in microbial infections; ii) to develop a two stages in vivo protocol for assessment of drug efficacy, with a first screening in the invertebrate
G.mellonella
and a second validation in mouse; iii) to asses the usefulness of nanocarriers delivery in terms of drug uptake, microbial interaction and tissue delivery.