How the molecular weight affects the in vivo fate of exogenous hyaluronan delivered intravenously: A stable-isotope labelling strategy
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
33858586
DOI
10.1016/j.carbpol.2021.117927
PII: S0144-8617(21)00314-3
Knihovny.cz E-resources
- Keywords
- Hyaluronan, Metabolism, Molecular weight, Pharmacokinetics, Stable isotope,
- MeSH
- Drug Elimination Routes MeSH
- Cartilage metabolism MeSH
- Cyclic ADP-Ribose metabolism MeSH
- Administration, Intravenous MeSH
- Isotope Labeling methods MeSH
- Carbon Isotopes chemistry metabolism pharmacokinetics MeSH
- Bone and Bones metabolism MeSH
- Hyaluronic Acid chemistry metabolism pharmacokinetics MeSH
- Molecular Weight MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Tissue Distribution MeSH
- Uridine Diphosphate N-Acetylglucosamine metabolism MeSH
- Uridine Diphosphate Glucose metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Carbon-13 MeSH Browser
- Cyclic ADP-Ribose MeSH
- Carbon Isotopes MeSH
- Hyaluronic Acid MeSH
- Uridine Diphosphate N-Acetylglucosamine MeSH
- Uridine Diphosphate Glucose MeSH
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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