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 M, C-labelled HA of five Ms from 13.6-1562 kDa was prepared and administered to mice at doses 25-50 mg kg. The elimination efficiency increased with decreasing M. Low M hyaluronan was rapidly eliminated as small hyaluronan fragments in urine, while high M hyaluronan exhibited saturable kinetics and complete metabolization within 48 h. All tested Ms exhibited a similar uptake by liver cells and metabolization into activated sugars. C-labelling combined with LC-MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.