Abstract 5528: Toxicology and drug delivery by Cucurbit[n]urils and derivatives

Abstract

Drug candidates are continuously being discovered using high-through put screens of small compound chemical libraries, however, many of these drugs are not pursued into development because of low bioavailability. Therefore, drug delivery systems that improve bioavailability are of great importance. Cucurbit[n]urils (CB[n]) are a new class of molecular container compounds that are beginning to show great promise as a novel drug delivery system. Here we analyzed the toxicology of two unmodified cucurbit[n]urils, (CB[5] and CB[7]), and three CB[n] derivatives (Pentamer, Me-Hexamer and Ph-Hexamer). All five containers showed high cell tolerance at concentrations of up to 1mM in HEK293, HepG2 and RAW264.7 cell lines using assays for metabolic activity and cytotoxicity. We also studied uptake, and bioactivity using CB[7], the most soluble of the containers presented above. Bioactivity assays conducted with RAW264.7 cells infected with M. Smegmatis showed no inhibition of the activity of the antituberculosis drug ethambutol (EMB) by CB[7] after 3 days of incubation. This study provides a proof of principle towards the use of these containers as a novel drug delivery system. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5528.