Pharmacological studies of RGTA_(11), a heparan sulfate mimetic polymer, efficient on muscle regeneration

摘要

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 mm, 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.