The crucial role of spacer groups in macromolecular prodrug design

Conventional chemotherapy has been limited by a lack of cell specificity, resulting in unwanted peripheral toxicities and low therapeutic efficiency. In an attempt to overcome these problems, a variety of systems have been designed which are able to deliver the drug more effectively to the target site. Watersoluble macromolecular prodrugs, covalently linking the drug through a degradable spacer, constitute an interesting possibility. The linker plays a crucial role and must fulfil certain requirements in order to release the free parent drug in the vinicity of the tumor. This review will discuss some general principles related to the design of such polymeric drug carriers and an overview of the effect of the type of spacer on the rate of drug release and the correlated in vitro and in vivo results will be outlined.