Polymer therapeutics: Polymers as drugs, drug and protein conjugates and gene delivery systems: Past, present and future opportunities

As the 21st century begins we are witnessing a paradigm shift in medical practice. Whereas the use of polymers in biomedical materials applications - for example, as prostheses, medical devices, contact lenses, dental materials and pharmaceutical excipients - is long established, polymer-based medicines have only recently entered routine clinical practice [1-4]. Importantly, many of the innovative polymer-based therapeutics once dismissed as interesting but impractical scientific curiosities have now shown that they can satisfy the stringent requirements of industrial development and regulatory authority approval. The latter demand on one hand a cost-effective and profitable medicine or diagnostic, and on the other hand, a safe and efficacious profile that justifies administration to patients. The first clinical proof of concept with polymer therapeutics has coincided with the explosion of interest in the fashionable area called "nanotechnology". This has resulted in exponential growth in the field, and an increasing number of polymer chemists are turning their attention to the "bio-nano" arena. An attempt to define "nanotechnology" is beyond the scope of this review, but suffice it to say there is widespread agreement that application of nanotechnology to medicine, either via miniaturisation or synthetic polymer and supramolecular chemistry to construct nano-sized assemblies [5,61, offers a unique opportunity to design improved diagnostics, preventative medicines, and more efficacious treatments of life-threatening and debilitating diseases. It is thus timely for this volume of Advances in Polymer Science to review the field that has been named "polymer therapeutics" (Fig. 1). The term "polymer therapeutics" [1] has been adopted to encompass several families of constructs all using water-soluble polymers as components for design; polymeric drugs [3, 7], polymer-drug conjugates ( 1, 8], polymer-protein conjugates [2, 9], polymeric micelles to which a drug is covalently bound [10], and those multi-component polyplexes being developed as non-viral vectors [11]. From an industrial standpoint, these nanosized medicines are more like new chemical entities than conventional "drug-delivery systems or formulations" which simply entrap, solubilise or control drug release without resorting to chemical conjugation. In this issue of Advances in Polymer Science, the current status of those technologies in preclinical and clinical development is reviewed, together with presentation of an emerging area of novel synthetic chemistry - the new field of polymer genomics - and also a description of some of the sophisticated analytical methods being developed to characterise complex polymer constructs.