Polymeric sustained local drug delivery system for the prevention of vascular intimal hyperplasia

Abstract

Anastomotic intimal hyperplasia (IH) is a major cause of both autologous vein and synthetic vascular graft failure. We have previously published data suggesting that cyclosporin may reduce the development of IH in a canine model. However, systemic administration of cyclosporin could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporin from a polymeric vascular wrap will prevent the development of IH. To test this hypothesis, we developed a controlled release vascular wrap (sheet/ring) using a poly(ethylene glycol) (PEG) hydrogel. Sterilization of the polymers was performed using the ethylene oxide and hydrogen peroxide sterilization methods. It was found that except for one combination (8000 molecular weight and 1:1 crosslinking ratio), the differences in the swelling ratios for the sterilized and unsterilized hydrogels were not statistically significant. Release studies from unsterilized and ethylene oxide-sterilized PEG hydrogels were conducted. It was found that release lasted for approximately 50 h for sterilized as well as unsterilized PEG hydrogels. Acute animal studies, to test the deployment of both the polymeric sheets and rings to the adventitial surface of native arteries and veins, were completed successfully.

Improving delivery of hydrophobic drugs from hydrogels through cyclodextrins

“…3). In a previous study, 19 we have shown that the differences in swelling characteristics of a 3350 MW 1:1 unsterilized and sterilized PEG hydrogel were not statistically significant. Statistical significance was achieved for 8000 MW 1:1 PEG hydrogels with the EtO-sterilized PEG hydrogels having a lower swelling ratio compared with the unsterilized ones and the hydrogen peroxide-sterilized PEG hydrogels had a statistically significant higher swelling ratio compared with the unsterilized gels.…”

“…43 It has to be noted that this effect on the release characteristics would be dependent, on a large part, on the type of drug molecule involved. A prior study 19 involving a dye, rhodamine, did not exhibit any differences in the release trends from these hydrogel networks upon sterilization. Because of the effects that the sterilization procedure had on the release characteristics of CyA, it was hypothesized that a cyclodextrin-CyA inclusion complex would be able to protect the CyA molecule and hence shield the molecule from any such interactions that it might have with the sterilized gel.…”

Statins therapy: a review on conventional and novel formulation approaches

“…Initially, the PolyRing device was developed for the targeted delivery of the drug cyclosporine A for the treatment of vascular intimal hyperplasia (IH). [97] In this application, drug was encapsulated within the microspheres, which were in turn embedded in a PEG block as a polymeric vascular wrap, termed the 'PolyRing'. Statins can be other potent agents with antiproliferative properties, suggested for the inhibition of IH as statins have a more direct route for the inhibition of smooth muscle cell.…”

In Situ Bioengineering of Arterial Vein Grafts

“…Kanjickal et al used a poly(ethylene glycol) hydrogel for sustained local delivery of cyclosporine to AVGs, and successfully reduced anastomotic IH development [240]. In another study, Cagiannos et al used a polytetrafluoroethylene sheath to locally deliver rapamycin (sirolimus) to AVGs, and effectively reduced anastomotic IH in a pig model [241].…”

“…Hz as described in Section 2.3.3. pO 2 , pCO 2 , pH, perfusate temperature, and bathing media temperature were measured within each loop of the paired EVPS every hour. After each perfusion experiment, the unpressurized vessel dimensions were measured from rings cut from the proximal and distal ends of the PIJV sengments using a custom-designed "chuck" as described in Brant et al [240]. The values obtained from each ring were then averaged, and these measurements were then used with the pressurized outer diameter and intraluminal pressure measurements to calculate the CWS as described in Section 2.5.4.…”