‘Collagen Vitrigel Sheet’ as a Novel Drug Delivery Bio-material

Abstract

Background/Aims. Ischemia/reperfusion (I/R)- induced injury is an acute injury mainly caused by surgical procedures. And HGF (hepatocyte growth factor) is known to protect against I/R-injury effectively. The sufficient dose of HGF must be topically delivered to the target organ to minimize the organ damage on surgery (reperfusion) and the dose of drug. For this purpose, we developed a novel technology for converting a fragile disk of the conventional type-I collagen gel into a strong and transparent ‘vitrigel membrane’, based on a concept for the vitrification of heat-denatured proteins.

In the present study, we examined the efficacy of the newly designed ‘HGF-containing collagen vitrigel sheet’ as an effective drug delivery system in mouse liver I/R model.

Materials and methods. Male C57Black6 mice were subjected to 60 min-liver ischemia (middle and left liver lobes) and reperfusion. Immediately after liver ischemia, the ischemic liver lobes were covered by collagen vitrigel sheet containing hHGF (3..g/ml). Reperfused liver injury was evaluated by biochemical/histological methods and bio-imaging of hepatic oxidative stress (redox-sensitive GFP probe) and apoptosis (bioluminescent caspase-3 activity probe).

Results. Collagen vitrigel sheet (containing hHGF) released hHGF until 96 hr in vitro and successfully delivered hHGF to the liver tissue suffering I/R. This effectively protected liver from I/R-induced injury. Blood biochemistry showed reduced levels of serum GOT/GPT/LDH, and liver histology revealed reduced necrotic area in the hHGF-treated liver. Oxidative stress and caspase-3 activity of the liver were examined by bioimaging, which revealed that hHGF delivered by vitrigel sheet significantly reduced oxidative stress and apoptotic cell death in the post-ischemic liver.

Conclusions. hHGF-containing collagen vitrigel sheet protected liver from I/R-induced injury. Collagen vitrigel sheet may have good therapeutic potential in topical drug delivery in various clinical settings.

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