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

The purpose of this study was to determine the absorption, distribution and excretion of (99m)technetium-labeled, high-molecular-weight hyaluronan ((Tc-99m-HA) and (99m)technetium pertechnetate (Tc-99m-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized Tc-99m-HA alone, and a second confirmatory study compared uptake of labeled Tc-99m-HA with Tc-99m-P. Urinary and fecal excretion after Tc-99m-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 Tc-99m-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from Tc-99m-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from Tc-99m-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 Tc-99m-HA, but not from Tc-99m-P. Conversely, absorption, distribution and excretion of Tc-99m was completely different from Tc-99m-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.