Conclusion & Future Perspective
As we are living in a changing society and life expectancy has been continuously increasing, human pathologies related to aging, such as musculoskeletal disorders, arthritis, nonhealing wounds or neurodegenerative diseases, are becoming major health problems. Therefore, a switch in the therapeutic armory is urgently required. There is a need to identify and also validate key molecular targets that could provide novel strategies, and following this to develop novel therapies. The high versatility of polymer conjugates allows the design of effective treatments for these human pathologies. However, many challenges still remain before these novel nanopharmaceuticals can achieve routine clinical use.
In achieving clinical proof of concept, many lessons have been learnt from the development of conjugates with orthodox anticancer agents.[5] This has generated a strong knowledge that will help to overcome the remaining challenges in the application of macromolecular therapeutics to novel molecular targets, not only in cancer therapy but also in a much broader range of diseases. In this context, and particularly exciting, will be the use of nanoconjugates as tools to promote tissue repair or tissue protection during injury.
The future of cancer therapy will mainly rely on specific targets and in most cases in their combination, in order to achieve more selectivity, efficacy and lower toxicity.[35,141] On the other hand, the action on one target could result in the treatment of more than one disease due to crosstalk molecular mechanisms. It is imperative to better understand the molecular bases of disease; this will help to better design conjugate therapeutics with adequate pharmacokinetics at whole organism as well as at cellular level. Therefore, polymer architecture, conjugate conformation and bioresponsiveness in selected physiological conditions can be taken as key features to be adequately modulated by scientists to achieve therapeutic benefit.[33] Successful active targeting by introducing specific moieties on the polymer carrier it has been difficult to demonstrate in clinical settings, mainly due to the lack of awareness for the appropriate overexpressed disease cell receptor to target, but in some cases this limitation is readily surpassed.[142] It is also essential to consider early on the issues relating to potential toxicology, industrial feasibility, product identity validation and clinical trial design, whilst maintaining awareness of product approval mechanisms used by the regulatory agencies.[34] Thus, the importance of interdisciplinary work must not be overlooked, whereby close collaboration between biologists, medical doctors, chemists, regulators and industry can lead to benefits for human welfare.
Most of the examples presented here are still at an early stage of preclinical development, but these and other novel approaches underline a strong research base for future polymer therapeutics, which will hopefully reach clinical use in the next decade.
Nanomedicine. 2010;5(6):915-935. © 2010 Future Medicine Ltd.
Cite this: Polymer–Drug Conjugates for Novel Molecular Targets - Medscape - Aug 01, 2010.
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