Pharmacological studies of RGTA(11), a heparan sulfate mimetic polymer, efficient on muscle regeneration.
RGTA is a family of chemically modified polymers that have been engineered to mimic the properties of heparan sulfates towards heparin binding growth factors. In vivo, RGTA stimulated tissue repair and protection when injected at the site of an injury. These properties have been reported in various models, suggesting a potential interest for therapeutic uses as a general tissue repair agent. We have focused our interest on RGTA(11), a dextran derivative that was shown to enhance, after a unique and local administration, muscle regeneration after total crushing. We first show that a single RGTA(11) systemic administration can be as efficient as a local injection for stimulating muscle regeneration. Using an H(3)-labeled RGTA(11) we have measured some pharmacokinetic parameters. Distribution volume was 51.81 mL, clearance was about 2 mL/min, and half-life was 94 min, giving a total elimination time of 11 h. We also demonstrate that RGTA(11) remains detectable in the body only after tissue injury. It was detected by autoradiography in the crushed muscle just after injury and remained at least for a week. These results provide a rational explanation for the long lasting effect of a single local or systemic injection of RGTA.
Meddahi
Anne
A
Laboratoire de Recherche sur la Croissance et la Régénération Tissulaires (CRRET), UPRESA CNRS 7053, Université Paris XII-Val de Marne, 61 avenue du Général de Gaulle, 94010 Créteil, France.
Brée
Françoise
F
Papy-Garcia
Dulce
D
Gautron
Jean
J
Barritault
Denis
D
Caruelle
Jean-Pierre
JP
D000818:Animals; D001345:Autoradiography; D003911:Dextrans / Q000493:pharmacokinetics / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D014316:Tritium / Q000737:chemistry / Q000378:metabolism
D003911:Dextrans; D006497:Heparan Sulfate; D014316:Tritium; C104129:RGTA11