Pro-Drugs

  

A novel approach towards drug delivery is via the use of Pro-Drugs. Pro-drugs
are derivatives of regular drugs, modified for one or more of the
following factors:

• The drug by itself may have a very short half-life. Thus by attaching it to a polymer as a sidechain, the half-life of the drug may be improved.
  
• The drug action site may be subject to frequent physiological changes, which may reduce the residence time of the drug at the targetted site. Derivatizing the drug our attaching it to a suitable polymer may improve its residence time. For example, a drug that is required to treat IBDs often faces the problem of low residence time due to the frequency of mucus turn-overs. Thus by attaching this drug to a bioadhesive polymer (or more specifically a mucoadhesive polymer) may improve its residence time in the stomach.
  
• A drug may be derivatized so as to make it lipophilic and hence allow its transfer across the blood brain barrier.
  
• Derivatization of the drug can make it site-specific and can aid tumor targetting.
  

  The most popular form of pro-drugs are the pendant type of drug delivery
  systems, where the drug is attached as a side chain to the polymer matrix via
  a biodegradable bond. This bond may be hydrolysable (ester, anhydride) or
  enzymatically biodegradable (amide). Pendant drug delivery systems mainly
  aid in increasing the half-life of the drug as well as the residence time at the
  affected site. Such systems have been vastly studied and reviewed in the
  literature (Heller, 1990).

  Another emerging technology for pro-drugs has been pioneered by Prof. Bodor's
  group in Univ. of Florida and this involves a Redox based chemical delivery
  system. The drug is attached to a small molecule which makes it lipophillic
  and allows its passage across various biological membranes (the toughest of
  these membranes is the blood brain barrier). Once the pro-drug is across
  the biological membrane, the active form of the drug gets released by way
  of Reduction-Oxidation type of reactions. The most well-studied type of this
  concept is the pyridine-pyridinium based pro-drugs developed by Bodor and
  co-workers.

  Related Links

  
  Dr. Ron Borchardt, UKans
  
  
  Dr. Nick Bodor, UFl
  This page is currently in development and soon will feature links to the groups
  working on chemical delivery systems as well as some relevant references.
  Stay tuned