The Folate Pro-drug Approach

Recently it was shown that folate transport from the basolateral site occurs as readily as that from the luminal site, indicating that changes in secretion can mediate excess urinary folate excretion [56]. 

It has been hypothesized that folate receptor-mediated endocytosis can be exploited for the selective delivery of drugs by covalent attachment to folate via its y-carboxyl group. This concept was primarily designed for the targeting of various biomolecules to solid tumours. For a 

Interestingly, after intravenous administration of a radiolabelled folate conjugate ( -In-dium-diethylenetriaminepenta acid (DTPA)-folate) in the rat, the conjugate was rapidly excreted in the urine. Moreover, after intravenous administration to athymic mice with a human tumour cell implant, the radiotracer was not only taken up by the subcutaneous tumour but was also taken up by the kidneys in significant quantities [63], indicating substantial renal selectivity of the folate conjugate. In addition to the kidney, the liver also has a high concentration of the folate-receptor [64]. 

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