One of the main challenges with new pharmaceuticals is delivery. Many drugs that display high activity are lipophilic; however, to deliver these molecules, they must also be hydrophilic. One method to increase the aqueous solubility of pharmaceuticals is through the utilization of cyclic chlorophosphazenes as a drug delivery system. Cyclophosphazenes are a model system for this delivery for several reasons, one being the ease at which the phosphorus atoms of the ring structure can be substituted with a wide variety of side groups. We have synthesized a hydrophilic phosphazene-based system by substituting three equivalents of tetraethyleneglycol monomethyl ether (TEGME) onto the phosphazene trimer ring ([PCl2N]3). Following the addition of TEGME, the phosphazene rings system contains additional sites for further modification and substitution. These sites can be substituted with imaging agents, anti-cancer agents, and targeting moieties. Imidazoles have recently garnered much attention and have been shown to be effective as anti-cancer and anti-microbial agents; however, they suffer from low aqueous solubility. The previously synthesized phosphazene system can be used to enhance the solubility of imidazoles, making them a viable drug candidate. Additionally, we have been investigating the efficacy of coumarins as imagining agents as well as incorporating targeting moieties (triphenylphosphonium cations) to the previously synthesized phosphazene system. Triphenylphosphonium-based compounds have demonstrated effectiveness in targeting mitochondria in cancer cells. By substituting triphenylphosphonium cations to the cyclophosphazene system, the efficacy of the compound may increase while also decreasing toxicity. Finally, coumarins have been widely used in the fields of chemistry, biology, and medicine and contain unique photophysical properties including high quantum yield as well as high stability and biological compatibility. Preliminary studies have shown that a variety of coumarins have been successfully substituted onto the phosphazene trimer ring. Results from these studies have been characterized via fluorescent spectroscopy as well as multinuclear NMR studies.

Substituted phosphazenes as drug deilvery systems

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