Advancing PROTAC Delivery: Liposomal, NAB, and Cyclodextrin-Based Formulations of ACBI2

PROTACs (PROteolysis-Targeting Chimeras) are a novel drug class enabling selective target protein degradation [1,2].
However, their challenging physicochemical properties are a main hurdle for clinical translation.
Due to their heterobifunctional structure, PROTACs are large (~1 kDa) and polar, requiring tailored delivery systems [1,2]. ACBI2, the PROTAC used in this study, is a 'beyond rule of 5' drug with no detectable water solubility [3]. We developed and optimized liposomal, NAB (nanoparticle albumin-bound), and cyclodextrin-based formulations of ACBI2 and tested them in vitro.