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Perivascular Drug Delivery Systems for the Inhibition of Intimal Hyperplasia

Kanjickal, Deenu George
http://rave.ohiolink.edu/etdc/view?acc_num=akron1133715441

Abstract Details

2005, Doctor of Philosophy, University of Akron, Chemical Engineering.
The long-term clinical success of autologous vein and synthetic vascular grafts is limited due to the development of anastomotic intimal hyperplasia (IH). Previously published data suggests that cyclosporine (CyA) (an immunosuppressive drug) may reduce the development of IH in a canine model [1]. However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporine from a polymeric vascular wrap will prevent the development of IH. In order to test this hypothesis, we developed three controlled release polymeric devices that could be placed around vascular graft anastomotic sites to deliver therapeutic drugs locally. The first device is a poly(ethylene glycol) (PEG) hydrogel sheet. The second device is a composite device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres dispersed in the PEG hydrogel sheet. The third device is in the form of a ring (referred to as PolyRing from here on) that can be slipped around the anastomotic sites. PolyRing is a composite polymeric device consisting of PLGA microspheres embedded in a PEG hydrogel. In-vitro studies were conducted on the three devices to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice. In-vivo studies were conducted on a swine model to evaluate the biocompatibility, drug optimization and efficacy of PolyRing. The biocompatibility study utilized four (4) domestic swine with non-drug loaded PolyRings harvested at two (2) and four (4) week time points. PolyRings (ID 3-5 mm; OD 7-8 mm; Length 5 mm) were implanted in subcutaneous and muscular tissues and around jugular veins and carotid arteries. The histological findings of gamma sterilized PolyRing implants at two and four weeks demonstrated the biocompatibility of this device. A minimal foreign body reaction with macrophages and foreign body giant cells was identified at the tissue/material surfaces at both two and four week implantation periods. This is a normal and expected finding for biocompatible materials. The drug optimization study utilized three (3) domestic swine with CyA-loaded PolyRings harvested at one (1) week. The drug loaded PolyRings were implanted around jugular veins and carotid arteries. The drug optimization studies revealed a proportional increase in the concentration of CyA in tissue with the concentrations of the drug loaded within PolyRing. The systemic circulation showed concentrations less than the sensitivity of the assay (25 ng/ml). Hence, we were able to achieve truly local concentrations of the drug using the device PolyRing.
Stephanie Lopina (Advisor)
193 p.
perivascular drug delivery device; intimal hyperplasia; controlled drug delivery; poly(ethylene glycol) (PEG) hydrogel; poly(lactide-co-glycolide) (PLGA) microspheres; biocompatibility; tissue culture; cyclosporine (CyA); PolyRing

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Citations

  • Kanjickal, D. G. (2005). Perivascular Drug Delivery Systems for the Inhibition of Intimal Hyperplasia [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1133715441

    APA Style (7th edition)

  • Kanjickal, Deenu. Perivascular Drug Delivery Systems for the Inhibition of Intimal Hyperplasia. 2005. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1133715441.

    MLA Style (8th edition)

  • Kanjickal, Deenu. "Perivascular Drug Delivery Systems for the Inhibition of Intimal Hyperplasia." Doctoral dissertation, University of Akron, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=akron1133715441

    Chicago Manual of Style (17th edition)

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© 2005, all rights reserved.
This open access ETD is published by University of Akron and OhioLINK.