Intra-Articular Hyaluronic Acid and Chondroitin Sulfate: Pharmacokinetic Investigation in Osteoarthritic Rat Models.
Journal
Current therapeutic research, clinical and experimental
ISSN: 0011-393X
Titre abrégé: Curr Ther Res Clin Exp
Pays: United States
ID NLM: 0372621
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
09
2019
accepted:
03
12
2019
entrez:
21
1
2020
pubmed:
21
1
2020
medline:
21
1
2020
Statut:
epublish
Résumé
Viscosupplementation of synovial fluid with intra-articular (IA) injections of hyaluronic acid (HA) is widely used for symptomatic treatment of osteoarthritis (OA). Herein we present HCS, a new combination of chemicals, associating HA and chondroitin sulfate (CS), both members of the glycosaminoglycan (GAGs) family, which are major components of the joint. HA provides viscosity to the synovial fluid and CS provides elasticity to the cartilage. Reduced levels of HA and CS are observed in OA joints and are associated with progressive cartilage damage and loss. The objective of the study was to evaluate the pharmacokinetic (PK) properties of both HA and CS after IA administration in a validated OA animal model. Motion impairment measurements and histological examinations were used to validate the ability of an IA injection of mono-iodoacetate (MIA) in the knee of rats to induce OA symptoms. Then, the PK properties of HA and CS after IA administration were characterized and each active ingredient was independently profiled: HA was labeled with tritium (3H-HA) and CS was labeled with carbon 14. (14C-CS) The final radio-labeled solution reproduced the cold HCS formulation. Four male Sprague-Dawley rats received a 1 mg MIA injection on day 1, then motor impairment was monitored from day 4 to day 18. Chondrocyte necrosis, loss of GAGs and other cartilage damage were observed. Twelve other rats received a MIA IA injection on day 1 then a radio-labeled HCS IA injection (50 µL) on day 8. Plasma and knee cartilage were collected postadministration and the terminal half-life was similar in both matrices (about 5 days), for both 3H-HA and 14C-CS. Despite differences in their molecular size, HA and CS showed PK behavior similarly characterized by prolonged residence inside the joint and slow release in plasma, favoring long-term beneficial effects. (
Sections du résumé
BACKGROUND
BACKGROUND
Viscosupplementation of synovial fluid with intra-articular (IA) injections of hyaluronic acid (HA) is widely used for symptomatic treatment of osteoarthritis (OA). Herein we present HCS, a new combination of chemicals, associating HA and chondroitin sulfate (CS), both members of the glycosaminoglycan (GAGs) family, which are major components of the joint. HA provides viscosity to the synovial fluid and CS provides elasticity to the cartilage. Reduced levels of HA and CS are observed in OA joints and are associated with progressive cartilage damage and loss.
OBJECTIVE
OBJECTIVE
The objective of the study was to evaluate the pharmacokinetic (PK) properties of both HA and CS after IA administration in a validated OA animal model.
METHODS
METHODS
Motion impairment measurements and histological examinations were used to validate the ability of an IA injection of mono-iodoacetate (MIA) in the knee of rats to induce OA symptoms. Then, the PK properties of HA and CS after IA administration were characterized and each active ingredient was independently profiled: HA was labeled with tritium (3H-HA) and CS was labeled with carbon 14. (14C-CS) The final radio-labeled solution reproduced the cold HCS formulation.
RESULTS
RESULTS
Four male Sprague-Dawley rats received a 1 mg MIA injection on day 1, then motor impairment was monitored from day 4 to day 18. Chondrocyte necrosis, loss of GAGs and other cartilage damage were observed. Twelve other rats received a MIA IA injection on day 1 then a radio-labeled HCS IA injection (50 µL) on day 8. Plasma and knee cartilage were collected postadministration and the terminal half-life was similar in both matrices (about 5 days), for both 3H-HA and 14C-CS.
CONCLUSIONS
CONCLUSIONS
Despite differences in their molecular size, HA and CS showed PK behavior similarly characterized by prolonged residence inside the joint and slow release in plasma, favoring long-term beneficial effects. (
Identifiants
pubmed: 31956378
doi: 10.1016/j.curtheres.2019.100573
pii: S0011-393X(19)30022-0
pii: 100573
pmc: PMC6957868
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100573Informations de copyright
© 2019 LCA Pharmaceutical, Chartres, France.
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