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Macromolecular therapeutics: advantages and prospects with special emphasis on solid tumour targeting.

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-alpha-2a. This article discusses these and other polymeric drugs in the setting of targeting to solid tumours.