Gallium Maltolate - Therapeutic Activity

Therapeutic Activity

Gallium maltolate is able to deliver gallium with high oral bioavailability: the bioavailability is several times higher than that of gallium salts such as gallium nitrate and gallium trichloride. Gallium is antiproliferative to pathologically proliferating cells, particularly cancer cells and some bacteria, due primarily to its ability to mimic ferric iron (Fe3+). Ferric iron is essential for DNA synthesis, as it is present in the active site of the enzyme ribonucleotide reductase, which catalyzes the conversion of ribonucleotides to the deoxyribonucleotides required for DNA. Gallium is taken up by the rapidly proliferating cells, but it is not functional for DNA synthesis, so the cells cannot reproduce and they ultimately die by apoptosis. Normally reproducing cells take up little gallium (as is known from gallium scans), and gallium is not incorporated into hemoglobin, accounting for the relatively low toxicity of gallium.

The anti-inflammatory activity of gallium appears to involve the down-regulation of inflammatory T cells and macrophages, as well as possible interference with matrix metalloproteinases. Because many iron compounds are pro-inflammatory, the ability of gallium to act as a non-functional iron mimic may contribute to its anti-inflammatory activity.

Analgesic activity has also been reported for gallium maltolate. Orally administered gallium maltolate has alleviated cancer-related pain, and topically applied gallium maltolate, at doses one-thousandth those of the safe oral doses, has been effective against refractory neuropathic pain (severe postherpetic neuralgia). The analgesic activity likely derives from gallium's observed anti-inflammatory mechanisms, and possibly from its interactions with certain matrix metalloproteinases and substance P, whose activities are zinc-mediated and which have been implicated in the etiology of pain.