Size optimization of carfilzomib nanocrystals for systemic delivery to solid tumors.

ABSTRACT: Carfilzomib (CFZ) is a second-generation proteasome inhibitor effective in blood cancer therapy. However, CFZ has shown limited efficacy in solid tumor therapy due to the short half-life and poor tumor distribution. Albumin-coated nanocrystal (NC) formulation was shown to improve the circulation stability of CFZ, but its antitumor efficacy remained suboptimal. We hypothesize that NC size reduction is critical to the formulation safety and efficacy as the small size would decrease the distribution in the reticuloendothelial system (RES) and selectively increase the uptake by tumor cells. We controlled the size of CFZ-NCs by varying the production parameters in the crystallization-in-medium method and compared the size-reduced CFZ-NCs (z-average of 168 nm, NC₁₆₈) with a larger cou

SUBMITTER: Gadalla HH 

PROVIDER: S-EPMC9737058 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature