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, 2, 3, 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, 6], 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”  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 , and those multi-component polyplexes being developed as non-viral vectors . 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.
KeywordsProtein Conjugate Polymeric Drug Block Copolymer Micelle Deoxyribose Nucleic Acid HPMA Copolymer
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- 3.Dhal PK, Holmes-Farley SR, Mandeville WH, Neenan TX (2002) Polymeric drugs. In: Encyclopedia of Polymer Science and Technology, 3rd edn. Wiley, New York, pp 555–580 Google Scholar
- 4.Duncan R (2003) Polymer-drug conjugates. In: Budman D, Calvert H, Rowinsky E (eds) Handbook of Anticancer Drug Development. Lippincott, Williams & Wilkins, Philadelphia, pp 239–260 Google Scholar
- 5.Editorial. Nanomedicine: grounds for optimism. Lancet, pp 362, 673; (2004) NIH Roadmap for Nanomedicines, Willis RC (2004) Good things in small packages. Nanotech advances are producing mega-results in drug delivery. Modern Drug Discov p 30–36. European Science Foundation Policy Briefing (2005) ESF Scientific Forward Look on Nanomedicine 23 February 2005 ( http://www.esf.org )
- 7.Gebelein CG, Carraher CE (1985) Bioactive polymeric systems. Plenum, New York Google Scholar
- 8.Ringsdorf H (1975) Structure and properties of pharmacologically active polymers. Polym J Sci Polymer Symp 51:135–153 Google Scholar
- 13.Morawetz H (1985) Polymers: the origins and the growth of a science. Wiley, New York Google Scholar
- 14.Lehn JM (1995) Supramolecular chemistry: concepts and perspectives. Wiley, New York Google Scholar
- 16.Jatzkewitz H (1955) Peptamin (glycyl-L-leucyl-mescaline) bound to blood plasma expander (polyvinylpyrrolidone) as a new depot form of a biologically active primary amine (mescaline). Naturforsch Z 10b:27–31 Google Scholar
- 17.Breslow DS (1976) Biologically active synthetic polymers. Pure Appl Chem 46:103–13 Seymour LW (1991) Synthetic polymers with intrinsic anticancer activity. J Bioact Comp Polymers 6:178–216 Google Scholar
- 21.Duncan R (2003) Polymer-drug conjugates. In: Budman D, Calvert H, Rowinsky E (eds) Book of anticancer drug development. Lippincott, Williams & Wilkins, Philadelphia, pp 239–260 Google Scholar
- 24.Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nature Rev Drug Discov 4:581–593 Google Scholar
- 25.Duncan R, Kopecek J (1984) Soluble synthetic polymers as potential drug carriers. Adv Polymer Sci 57:51–101 Google Scholar
- 26.Bader H, Dorn K, Hupfer B, Ringsdorf H (1985) Polymeric monolayers and liposomes as models for biomembranes. How to bridge the gap between polymer science and membrane biology? Adv Polymer Sci 64:1–62 Google Scholar
- 28.Duncan R, Izzo L (2005) Dendrimer biocompatibility and toxicity. In: Florence AT (ed) Advanced drug delivery reviews special issue on dendrimers. in press Google Scholar