Publication details

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

Authors

ŠIMEK Matěj NEŠPOROVÁ Kristina KOCURKOVÁ Anna FOGLOVÁ Tereza AMBROŽOVÁ Gabriela VELEBNÝ Vladimír KUBALA Lukáš HERMANNOVÁ Martina

Year of publication 2021
Type Article in Periodical
Magazine / Source Carbohydrate Polymers
MU Faculty or unit

Faculty of Science

Citation
web https://doi.org/10.1016/j.carbpol.2021.117927
Doi http://dx.doi.org/10.1016/j.carbpol.2021.117927
Keywords Hyaluronan; Pharmacokinetics; Molecular weight; Stable isotope; Metabolism
Description 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. 13C-labelling combined with LC–MS provides an excellent approach to elucidating in vivo fate and biological activities of hyaluronan.

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