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Absorption, Uptake and Tissue Affinity of High-Molecular-Weight Hyaluronan after Oral Administration in Rats and Dogs

2008; American Chemical Society; Volume: 56; Issue: 22 Linguagem: Inglês

10.1021/jf8017029

1520-5118

Lajos Balogh, András Polyák, Domokos Máthé, Réka Király, Juliana Thuroczy, Marian Terez, Győző A. Jánoki, Yaoting Ting, Luke R. Bucci, Alexander G. Schauss,

Connective tissue disorders research

The purpose of this study was to determine the absorption, distribution and excretion of 99mtechnetium-labeled, high-molecular-weight hyaluronan ((99mTc-HA) and 99mtechnetium pertechnetate (99mTc-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized 99mTc-HA alone, and a second confirmatory study compared uptake of labeled 99mTc-HA with 99mTc-P. Urinary and fecal excretion after 99mTc-HA ingestion by rats showed 86.7−95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from 99mTc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from 99mTc-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from 99mTc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from 99mTc-HA, but not from 99mTc-P. Conversely, absorption, distribution and excretion of 99mTc was completely different from 99mTc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecular-weight HA.