Hydrolytic stability of carbamate and carbonate closomers for the design of a multifaceted drug delivery system

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Twelve-fold substituted polyhedral boranes (closomers) are of therapeutic and diagnostic interest in the applications of targeted drug delivery. These compounds consist of a core molecule with 12 vertices and allow for a high degree of multifaceted substitution. Our group has previously reported on ester and ether based closomers1, but more recently have been working with the more synthetically useful carbonate and carbamate based closomers. The solution based properties of these structures their relative stability towards acid and base hydrolysis were investigated for the purpose of determining the best structural design for drug delivery applications. Some of the these molecules have limited solubility in aqueous media, and thus a system for analyzing these compounds with accurate pH monitoring using a glass electrode was established using IUPAC standards.2 The devised system is applicable to any organic-aqueous solvent mixture, and can be applied with any standard glass electrode that is primarily utilized for aqueous conditions. The system corrects for any solvent effects due to the presence of the organic component by the utilization of the Debye-Huckel Extended Law. Preliminary studies show that the carbonate and carbamate bond at the polyhedral borane cage are hydrolytically stable in the pH 2-12 range. The stability of these core structures allows for a potentially much more tunable release system in drug delivery applications, and solidifies the use of carbamate based systems for selective release of the pharmaceutical payload.