A Novel Polymer-Coated Nanoparticle (Np) For Urothelium Penetration And Drug Delivery

e15543 Background: Up to 40% of patients with non-invasive bladder cancer (BC) will develop invasive disease progression despite locally-directed therapy. Overcoming the urothelial barrier is a challenge for intravesical drug delivery. We designed a biodegradable poly(lactide-co-glycolide) (PLGA) NP coated with a novel cell penetrating polymer, poly (guanidinium oxanorbornene) (PGON) for testing against BC in vitro and in vivo. We chose to deliver the HDAC inhibitor belinostat (bel) for its BC cell cytotoxicity and inhibition of invasion u0026 migration pathways; key mechanisms that enable progression of BC. Methods: Fluorophore (C6) or bel was encapsulated in PLGA using an oil/water nanoemulsion method, and surface coated with PGON, and then characterized for morphology, size, and loading. BC cell lines UM-UC-3 and T24 were treated with belinostat or NP-bel-PGON vs controls for assessment of cytotoxicity and acetyl-H4 histone expression over time. In vivo murine bladder and ex vivo human ureter were treated ...