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Macromolecular Therapeutics

Advantages and Prospects with Special Emphasis on Solid Tumour Targeting

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Abstract

Macromolecular drugs (also referred to as polymeric drugs) are a diverse group of drugs including polymer-conjugated drugs, polymeric micelles, liposomal drugs and solid phase depot formulations of various agents. In this review we will consider only water-soluble macromolecular drugs. In common, such drugs have high molecular weights, more than 40 kDa, which enables them to overcome renal excretion. Consequently, this group of drugs can attain prolonged plasma or local half-lives.

The prolonged circulating time of these macromolecules enables them to utilise the vascular abnormalities of solid tumour tissues, a phenomenon called the enhanced permeability and retention (EPR) effect. The EPR effect facilitates extravasation of polymeric drugs more selectively at tumour tissues, and this selective targeting to solid tumour tissues may lead to superior therapeutic benefits with fewer systemic adverse effects. This contrasts with conventional low-molecular-weight drugs, where intratumour concentration diminishes rapidly in parallel with plasma concentration. The EPR effect is also operative in inflammatory tissues, which justifies the development and use of this class of drugs in infectious and inflammatory conditions.

At the present time, several polymeric drugs have been approved by regulatory agencies. These include zinostatin stimalamer (copolymer styrene maleic acid-conjugated neocarzinostatin, or SMANCS) and polyethyleneglycol-conjugated interferon-α-2a. This article discusses these and other polymeric drugs in the setting of targeting to solid tumours.

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Notes

  1. Use of tradenames is for product identification only and does not imply endorsement

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Acknowledgements

As the authors, we would like to acknowledge our colleagues William Regalson, Toshimitsu Konno, Helmet Ringsdorf, Ruth Duncan, Shojiro Maki and Tomohiro Sawa, for their enthusiasm, collaboration and support of our work in various aspects of the subject matter. We would also like to express our thanks to Citus Books for granting the permission to reproduce figure 1 of this review. Hiroshi Maeda acknowledges the continuous support for cancer grant in aid from the Ministry of Education, Science, Culture and Technology of Japan.

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Authors and Affiliations

  1. Department of Microbiology, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto, 860-0811, Japan

    Khaled Greish, Jun Fang, Takao Inutsuka &  Hiroshi Maeda

  2. Department of Surgery I, Kumamoto University School of Medicine, Kumamoto, Japan

    Takao Inutsuka

  3. Kumamoto Junkanki-ka Hospital, Kumamoto, Japan

    Akinori Nagamitsu

Authors
  1. Khaled Greish
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  2. Jun Fang
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  3. Takao Inutsuka
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  4. Akinori Nagamitsu
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  5. Hiroshi Maeda
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Corresponding author

Correspondence to Hiroshi Maeda.

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Greish, K., Fang, J., Inutsuka, T. et al. Macromolecular Therapeutics. Clin Pharmacokinet 42, 1089–1105 (2003). https://doi.org/10.2165/00003088-200342130-00002

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  • DOI: https://doi.org/10.2165/00003088-200342130-00002

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