Predictable and tunable half-life extension of therapeutic agents by controlled chemical release from macromolecular conjugates.

ABSTRACT: Conjugation to macromolecular carriers is a proven strategy for improving the pharmacokinetics of drugs, with many stable polyethylene glycol conjugates having reached the market. Stable conjugates suffer several limitations: loss of drug potency due to conjugation, confining the drug to the extracellular space, and the requirement for a circulating conjugate. Current research is directed toward overcoming such limitations through releasable conjugates in which the drug is covalently linked to the carrier through a cleavable linker. Satisfactory linkers that provide predictable cleavage rates tunable over a wide time range that are useful for both circulating and noncirculating conjugates are not yet available. We describe such conjugation linkers on the basis of a nonenzymatic β-eliminati

SUBMITTER: Santi DV 

PROVIDER: S-EPMC3341049 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature