Aerosol Characterization, Toxicokinetic and Biodistribution Investigations Supporting Efficient Delivery of KIT2014 Peptide to the Airways in Mice after Nose-only Inhalation
Valentina Sala1 & Blane Stobbs2
1Kither Biotech Srl, Via Nizza 52, 10126 Torino, Italy
2Charles River Laboratories Edinburgh Ltd, Elphinstone Research Centre, EH33 2NE Tranent, United Kingdom
Summary
Proof-of-concept studies in vitro and in vivo have shown the therapeutic potential of KIT2014, a phosphoinositide 3-kinase gamma mimetic cell-permeable peptide, in the context of chronic obstructive respiratory diseases. Therefore, in accordance with international guidelines, inhalation studies in relevant species are needed to define the safety profile of KIT2014, to progress towards clinical development. This study enabled set up of the appropriate conditions to generate and characterize for the first time the aerosol features, biodistribution and bioavailability of respirable KIT2014 aerosol, suitable for nonclinical safety studies. The aerosol was generated by vibrating mesh nebulisers and administered to mice by nose-only flow past exposure system. Study results were pivotal to ensure feasibility of in vivo inhalation studies, and paved the way to follow-on GLP repeated dose studies