Research Project
8564720
The Hsp90 inhibitor 17-DMAG will be encapsulated in a nano-sized liposome formulation that is long-circulating with controlled drug release properties in tumor tissue. Reformulation of 17-DMAG in a nanoliposome will increase the dose intensity of 17-DMAG in solid tumors while reducing the hepatic, gastrointestinal, nausea and bone marrow toxicity. The key is devising a nanoliposome composition that will retain the drug in circulation and release the drug from the nanoliposome at an appropriate rate after accumulation in the tumor. ZoneOne Pharma will use a new class of sterol-modified lipids (SML) that enable a wide and predictable range of drug release rates from the nanoliposome to encapsulate 17-DMAG using a remote loading protocol. In this development plan, ZoneOne Pharma will design nanoliposome compositions of 17-DMAG for evaluation by loading efficiency, in vitro plasma stability, in vivo pharmacokinetic and biodistribution studies. These formulations will be evaluated for tumor release effect on therapeutic activity in a proof-of-concept efficacy study at the end of Phase 1. A single formulation will be selected from confirmation efficacy studies as the first step of a future Phase II project.
