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Prodrugs are medications that only activate once inside the body.  The conversion happens once the inactive drug is triggered.  The metabolized drug is then able to undergo its pharmacological activity.  Prodrugs can help reduce toxicity, increase bioavailability, reduce other drug interactions, and various other benefits.

Prodrugs are great for fighting cancerous tumors, especially when regular chemotherapy and radiation treatments are ineffective.  Oregon State University (OSU) exploits this concept to target carcinomas affecting the breast, lung, prostate, and colon.  Additionally lymphomas and sarcomas can be targeted.  OSU formulated lipid-based carriers (liposomes) to deliver the prodrug to the hypoxic region of the tumor.  The absence of oxygen initiates the metabolism of the drug converting the inactive form to the active form.

OSU has seen success in lung cancer tumor models in mice and dogs.  The lipid formulations show an obvious improvement in performance in tumor suppression over the same drug minus the liposome.  The liposomes increased the half-life from less than 30 minutes to greater than 9.5 and 5.5 hours (two lipid based formulations were tested, pegylated and non-pegylated polyethelene glycol).

The prodrug concept is being researched extensively in both small molecules and biologics.  We continue to see improvements in treatment and therapies to treat cancers and other diseases. 

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Sources:

World Pharma News: New drug delivery system shows promise for fighting solid tumors

Shah VM, Nguyen DX, Alfatease A, Bracha S, Alani AW.  Characterization of pegylated and non-pegylated liposomal formulation for the delivery of hypoxia activated vinblastine-N-oxide for the treatment of solid tumors.  J Control Release. 2017 Mar 14;253:37-45. doi: 10.1016/j.jconrel.2017.03.022.