Title:Drug Conjugates Using Different Dynamic Covalent Bonds and their Application in Cancer Therapy
VOLUME: 17 ISSUE: 7
Author(s):Panagiotis Theodosis-Nobelos, Despina Charalambous, Charalampos Triantis and Maria Rikkou-Kalourkoti*
Affiliation:Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia, Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia, Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia, Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia
Keywords:Polymer-drug conjugates, dynamic covalent bonds, anticancer pro-drugs, controlled drug delivery, targeted polymers,
degradable polymers.
Abstract:Polymer-drug conjugates are polymers with drug molecules chemically attached to polymer
side chains through either a weak (degradable bond) or a dynamic covalent bond. These systems are
known as pro-drugs in the inactive form when passing into the blood circulation system. When the prodrug
reaches the target organ, tissue or cell, the drug is activated by cleavage of the bond between the
drug and polymer, under certain conditions existing in the target organ. The advantages of polymer-drug
conjugates compared to other controlled-release carriers and conventional pharmaceutical formulations
are the increased drug loading capacity, prolonged in vivo circulation time, enhanced intercellular uptake,
better-controlled release, improved therapeutic efficacy, and enhanced permeability and retention
effect. The aim of the present review is the investigation of polymer-drug conjugates bearing anti-cancer
drugs. The polymer, through its side chains, is linked to the anti-cancer drugs via dynamic covalent
bonds, such as hydrazone/imine bonds, disulfide bonds, and boronate esters. These dynamic covalent
bonds are cleaved in conditions existing only in cancer cells and not in healthy ones. Thus, ensuring the
selective release of drug to the targeted tissue, reducing in this way, the frequent side effects of chemotherapy,
leading to a more targeted application, despite the nature of the applied polymer, possessing the
ability to aim tumors selectively via incorporation of a relative ligand.