How the molecular weight affects the in vivo fate of exogenous hyaluronan delivered intravenously: A stable-isotope labelling strategy

There is inconsistent information regarding the size effects of exogenously given hyaluronan on its in vivo fate. The data are often biased by the poor quality of hyaluronan and non-ideal labelling strategies used for resolving exogenous/endogenous hyaluronan, which only monitor the label and not hyaluronan itself. To overcome these drawbacks and establish the pharmacokinetics of intravenous hyaluronan in relation to its Mw, 13C-labelled HA of five Mws from 13.6?1562 kDa was prepared and administered to mice at doses 25-50 mg kg?1. The elimination efficiency increased with decreasing Mw. Low Mw hyaluronan was rapidly eliminated as small hyaluronan fragments in urine, while high Mw hyaluronan exhibited saturable kinetics and complete metabolization within 48 h. All tested Mws exhibited a similar uptake by liver cells and metabolization into activated sugars. 13Clabelling combined with LC?MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.

Automated summary

The in vivo fate of hyaluronan is influenced by its molecular weight, with low Mw hyaluronan being more efficiently eliminated while high Mw hyaluronan exhibits saturable kinetics. Hyaluronan is taken up by liver cells and metabolized into activated sugars in a similar manner regardless of its molecular weight. The use of 13C-labeling combined with LC-MS is an effective approach to studying the biological activities of hyaluronan.