Developmental and organ-specific toxicity of cucurbit[7]uril: in vivo study on zebrafish models

Huanxian Chen,Judy Y W Chan,Ruibing Wang,Donal H Macartney,Simon M Y Lee,Ian W Wyman,David Bardelang,Xue Yang

doi:10.1039/c5ra04335b

Abstract

The macrocyclic Cucurbit[7]uril was evaluated for itsin vivotoxicity profile, including developmental toxicity and organ-specific toxicities using zebrafish models.

Highlights

Macrocyclic host molecules such as the cyclodextrins and calixarenes have received considerable attention as vehicles for drug delivery, due to their ability to improve the water solubility, bioavailability, physical and chemical stability, and release pro les of drugs.1–4 During recent years a new family of macrocyclic host molecules, the cucurbit[n]urils (CB[n], n 1⁄4 5–8, 10, 14) have received increasingly intensive attention and have been the subject of a number of reviews due to their potential application in drug formulation and delivery.5,6 crooked bodies (CB)[n] consists of n glycoluril units that are bridged by 2n methylene groups, forming a hydrophobic cavity and two identical carbonyl-lined portals with negative dipole potentials
Examples of drugs which have been studied with CB[7] include: atenolol,11 pyrazinamide,12 platinum-based anti-cancer drugs such as cisplatin,13 prilocaine,14 coumarin,15 ranitidine,16 and vitamin B12 as well as coenzyme B12.17 For instance, we have reported the encapsulation of ranitidine by CB[7], and this encapsulation protected the drug from thermal degradation and could potentially extend the shelf-life of this drug
The lethal dose LD50 is likely around 750 mM for these 1 dpf zebra sh larvae

Summary

Introduction

Macrocyclic host molecules such as the cyclodextrins and calixarenes have received considerable attention as vehicles for drug delivery, due to their ability to improve the water solubility, bioavailability, physical and chemical stability, and release pro les of drugs. During recent years a new family of macrocyclic host molecules, the cucurbit[n]urils (CB[n], n 1⁄4 5–8, 10, 14) have received increasingly intensive attention and have been the subject of a number of reviews due to their potential application in drug formulation and delivery. CB[n] consists of n glycoluril units that are bridged by 2n methylene groups, forming a hydrophobic cavity and two identical carbonyl-lined portals with negative dipole potentials. During recent years a new family of macrocyclic host molecules, the cucurbit[n]urils (CB[n], n 1⁄4 5–8, 10, 14) have received increasingly intensive attention and have been the subject of a number of reviews due to their potential application in drug formulation and delivery.. In the years of 2000–2001, the research groups of Kim and Day independently isolated the homologues CB[5], CB[7] and CB[8], using a lower temperature of 75–90 C for the synthesis of these macrocycles.. In the years of 2000–2001, the research groups of Kim and Day independently isolated the homologues CB[5], CB[7] and CB[8], using a lower temperature of 75–90 C for the synthesis of these macrocycles.8,9 This development dramatically expanded the versatility of cucurbit[n]uril chemistry and has attracted more scientists to this eld. During the past een years, CB[n]s have demonstrated outstanding molecular recognition properties and superior interactions with a wide range of neutral and positively charged molecules, especially those possessing imine or amine groups, many of which are bioactive and medically relevant compounds.

Methods

Results

Conclusion