How the molecular weight affects the in vivo fate of exogenous hyaluronan delivered intravenously: A stable-isotope labelling strategy
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
33858586
DOI
10.1016/j.carbpol.2021.117927
PII: S0144-8617(21)00314-3
Knihovny.cz E-zdroje
- Klíčová slova
- Hyaluronan, Metabolism, Molecular weight, Pharmacokinetics, Stable isotope,
- MeSH
- cesty eliminace léčiva MeSH
- chrupavka metabolismus MeSH
- cyklická ADP-ribosa metabolismus MeSH
- intravenózní podání MeSH
- izotopové značení metody MeSH
- izotopy uhlíku chemie metabolismus farmakokinetika MeSH
- kosti a kostní tkáň metabolismus MeSH
- kyselina hyaluronová chemie metabolismus farmakokinetika MeSH
- molekulová hmotnost MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- tkáňová distribuce MeSH
- uridindifosfát-N-acetylglukosamin metabolismus MeSH
- uridindifosfátglukosa metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Carbon-13 MeSH Prohlížeč
- cyklická ADP-ribosa MeSH
- izotopy uhlíku MeSH
- kyselina hyaluronová MeSH
- uridindifosfát-N-acetylglukosamin MeSH
- uridindifosfátglukosa 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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