Prodrugs pp 379-416 | Cite as

Controlled Release - Macromolecular Prodrugs

  • Claus Larsen
  • Jesper Østergaard
  • Susan W. Larsen
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)


The majority of drug candidates have molecular weights of about 200–500 Dalton. Bioreversible derivatives obtained by covalent attachment of a promoiety similar in size to drug candidates can be referred to as low molecular weight prodrugs. This approach has been used to improve drug performance by overcoming various barriers to drug delivery. When the barrier is target site access and the target site can only be reached after transport via the systemic circulation, the in vivo fate of the drug/prodrug is affected by distribution processes, protein binding, and excretion, not to mention the range of metabolic reactions that prodrugs may undergo. The latter processes are influenced by the physicochemical properties of the prodrug derivative. However, these are less predictable when using the low molecular weight prodrug approach to optimize systemic sitespecific drug delivery. The macromolecular prodrug approach, in which the small therapeutic agent is attached to a macromolecular promoiety, has been exploited to provide drug targeting. The basic rationale behind this approach is that the transport properties of the macromolecular prodrug should be dictated predominantly by those of the macromolecular transport vector. Thus, macromolecular conjugates derived from a wide array of macromolecules endowed with intrinsic target receptor affinities, especially of anticancer agents and other therapeutics have been evaluated.


Drug Release Hyaluronic Acid Ethyl Benzoate Ester Prodrug Carbonate Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Claus Larsen
    • 1
  • Jesper Østergaard
    • 2
  • Susan W. Larsen
    • 1
  1. 1.Department of PharmaceuticsThe Danish University of Pharmaceutical SciencesDenmark
  2. 2.Department of Analytical ChemistryThe Danish University of Pharmaceutical SciencesDenmark

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