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Polymer therapeutics-prospects for 21st century: The end of the beginning

2012; Elsevier BV; Volume: 65; Issue: 1 Linguagem: Inglês

10.1016/j.addr.2012.08.012

1872-8294

Ruth Duncan, Marı́a J. Vicent,

Advanced biosensing and bioanalysis techniques

The term “polymer therapeutics” was coined to describe polymeric drugs, polymer conjugates of proteins, drugs and aptamers, together with those block copolymer micelles and multicomponent non-viral vectors which contain covalent linkages. These often complex, multicomponent constructs are actually “drugs” and “macromolecular prodrugs” in contrast to drug delivery systems that simply entrap (non-covalently) therapeutic agents. They have also been described as nanomedicines. First polymer–protein conjugates entered routine clinical use in 1990 and a growing number of polymeric drugs/sequestrants and PEGylated proteins/aptamers have since come into the market. Valuable lessons have been learnt over > 3 decades of clinical development, especially in relation to critical product attributes governing safety and efficacy, the validated methods needed for product characterisation. Not least there has been improved understanding of polymer therapeutic-specific biomarkers that will in future enable improved selection of patients for therapy. Advances in synthetic polymer chemistry (including control of 3D architecture), the move towards greater use of biodegradable polymers, polymers delivering combination therapy, increased understanding of polymer therapeutic critical product attributes to guide pharmaceutical development, and advances in understanding of endocytosis and intracellular trafficking pathways in health and disease are opening new opportunities for design and clinical use of polymer-based therapeutics in the decades to come.