To determine whether a polymer-drug conjugate might improve tumor cell kill compared to the corresponding unconjugated agent when used in combination with radiation, we examined the antitumor activity of a water-soluble conjugate of N-(4-hydroxyphenyl) retinamide (4HPR) and poly(L-glutamic acid), PG-4HPR, in lung cancer cells and xenografts. The antiproliferative activity of 4HPR and PG-4HPR in...

The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, ...

Colistin methanesulfonate (CMS) is the only prodrug of colistin available for clinical use for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Owing to its slow and variable release, an alternative is urgently required to improve effectiveness. Herein we describe a PEGylated colistin prodrug whereby the PEG is attached via a cleavable linker (col-aaPEG) i...

Acemetacin is the carboxymethyl ester of indomethacin and a pro-drug precursor compound, in other words, prodrug. The pharmacologically active metabolite acemetacin also indomethacin. exerts its potent non-steroidal anti-inflammatory effects body as It known that not only prodrug indomethacin, but an agent with gastric protective mechanisms, possibly involving reduction leukocyte adhesion, by e...

Effective chemotherapy remains a key issue for successful cancer treatment in general and neuroblastoma in particular. Here we report a chemotherapeutic strategy based on catalytic antibody-mediated prodrug activation. To study this approach in an animal model of neuroblastoma, we have synthesized prodrugs of etoposide, a drug widely used to treat this cancer in humans. The prodrug incorporates...

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...