Highly Water-Soluble Sulfonatopropoxylated Cucurbit[8]urils as Excipients for Drug Solubilization and Bioavailability Enhancement of Remdesivir

Abstract

A series of sulfonatopropoxylated cucurbit[8]uril derivatives (SPECB8s) with water-solubility ranging from 344 mmol/L to 360 mmol/L have been prepared. One of the derivatives SPE_5.5CB8 bearing an average of 5.5 sulfonatopropoxy side chains has been revealed to display high biocompatibility, with maximum tolerated dose being as high as 2500 mg/kg for mice. Phase solubility diagram investigations illustrate that SPE_5.5CB8 can solubilize eighteen poorly soluble drugs and, for fifteen of them including remdesivir, its solubilization efficiency is higher than that of Captisol, the most widely used β-cyclodextrin-derived excipient for drug formulation. Moreover, the improved solubilization for remdesivir, which is formulated by Captisol for clinical use, can lead to important increase of its antiviral activity as compared with Captisol.