How the molecular weight affects the in vivo fate of exogenous hyaluronan delivered intravenously: A stable-isotope labelling strategy
- Resource Type
- Authors
- Tereza Foglová; Gabriela Ambrožová; Anna Kocurková; Martina Hermannová; Matěj Šimek; Lukáš Kubala; Kristina Nešporová; Vladimír Velebný
- Source
- Carbohydrate polymers. 263
- Subject
- Uridine Diphosphate Glucose
Polymers and Plastics
Kinetics
Endogeny
02 engineering and technology
Drug Elimination Routes
010402 general chemistry
01 natural sciences
Poor quality
Bone and Bones
Pharmacokinetics
In vivo
Labelling
Materials Chemistry
Animals
Tissue Distribution
Hyaluronic Acid
Carbon Isotopes
Cyclic ADP-Ribose
Mice, Inbred BALB C
Uridine Diphosphate N-Acetylglucosamine
integumentary system
Stable isotope ratio
Chemistry
Organic Chemistry
Metabolism
021001 nanoscience & nanotechnology
0104 chemical sciences
carbohydrates (lipids)
Molecular Weight
Cartilage
Biochemistry
Isotope Labeling
Administration, Intravenous
Female
0210 nano-technology
- Language
- ISSN
- 1879-1344
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.