Theoretically, prodrugs are relatively noncytotoxic molecules, capable of being converted to cytotoxic species only at the site of the tumor, affording enhanced antitumor selectivity. One approach aimed at enhancing the selectivity of cancer chemotherapy for solid tumors relies on the application of prodrug-activating systems in suicide gene therapy. Enzyme-activating prodrug therapy, also know...

Bisphosphonates are used clinically to treat disorders of calcium metabolism and malignant bone disease and are known to inhibit cancer cell growth, adhesion, and invasion. However, clinical use of these agents for the treatment of extraskeletal disease is limited because of low cell permeability. We recently described a bisphosphonamidate prodrug strategy for efficient intracellular release of...

It is estimated that about 10% of the drugs approved worldwide can be classified as prodrugs. Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug. They are designed in order to improve the physicochemical, biopharmaceutical and/or pharmacokinetic properties...

We developed the novel polymeric prodrugs synthesized by mechanochemical solid-state copolymerization of glucose-based polysaccharides (dextran orglycogen) and the methacryloyloxy derivative of 5-fluorouracil (5-FU). The copolymerization proceededreadily and each polymeric prodrug was quantitatively obtained within8 h reaction. The number average molecular weight (Mn) and polydispersity (H) of ...

OBJECTIVES To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon-alpha combined with ribavirin in the treatment of chronic hepatitis C. DATA SOURCES Electronic databases, reference lists of retrieved reports, and the industry submissions to the National Institute for Clinical Excellence. REVIEW METHODS Sources were rigorously searched and studies were selected ...

Background Prodrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoin...

Several commonly used cancer chemotherapeutic prodrugs, including cyclophosphamide and ifosfamide, are metabolized in the liver by a cytochrome P450 (CYP)-catalyzed prodrug activation reaction that is required for therapeutic activity. Preclinical studies have shown that the chemosensitivity of tumors to these prodrugs can be dramatically increased by P450 gene transfer, which confers the capab...

Present work was inspired by an interesting finding of Raithel et al. (11) about remission of steroid-dependent, chronically active ulcerative colitis (UC) in a patient, after treatment with a combination of fexofenadine, disodium cromoglycate and an amino acid-based formula. Literature reports involvement of mast cells activation and increased histamine secretion in the pathogenesis of colitis...

Triblock copolymeric nanoreactors are introduced as an alternative for liposomes as encapsulating carrier for prodrug activating enzymes. Inosine-adenosine-guanosine preferring nucleoside hydrolase of Trypanosoma vivax, a potential prodrug activating enzyme, was encapsulated in nanometer-sized vesicles constructed of poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-(2-methyloxazoline)...