Work

Acidic Hydrolysis of N-Ethoxybenzylimidazoles (NEBIs): Potential Applications as pH-Sensitive Linkers for Drug Delivery

Year: 2007

Type: article

Abstract: This paper describes the development of a new class of N-linked imidazoles as potential pH-sensitive, cleavable linkers for use in cancer drug delivery systems. Kinetic analysis of eight derivatives of N-ethoxybenzylimidazoles (NEBIs) showed that their rates of hydrolysis are accelerated in mild aqueous acidic solutions compared to in solutions at normal, physiological pH. Incorporation of electron donating or electron withdrawing substituents on the phenyl ring of the NEBI resulted in the ability to tune the rates of hydrolysis under mild acidic conditions with half-lives ranging from minutes to months. A derivative of NEBI carrying doxorubicin, a widely used anticancer agent, also showed an increased rate of hydrolysis under mild acid compared to that at normal physiological pH. The doxorubicin analogue resulting from hydrolysis from the NEBI exhibited good cytotoxic activity when exposed to human ovarian cancer cells. These results demonstrate a potentially useful, general strategy for conjugating a wide range of drugs to imidazole-containing delivery vessels via NEBI functionalities for controlled release of therapeutics for drug delivery applications.

Source: Bioconjugate Chemistry

DOI: 10.1021/bc060224s

Authors: Seong Deok Kong, Alice Luong, Gerald Manorek, Stephen B. Howell, Jerry Yang

Institutions: University of California San Diego, Moores Cancer Center

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute