Doctoral thesis
OA Policy
English

Controlled drug delivery systems for perivascular application and intimal hyperplasia prevention

ContributorsMelnik, Tamara
Number of pages149
Imprimatur date2022-10-21
Defense date2022-10-17
Abstract

Intimal hyperplasia (IH) is a pathophysiological process developing in venous grafts, commonly used to bypass circulation blocked by atherosclerosis. IH causes graft failure with life-threatening consequences. IH occurs in three stages: hyper-acute, acute, and chronic over 6 to 8 weeks. The aim of the present thesis was to develop a perivascular drug delivery system for localized prevention of IH with atorvastatin. To increase the residence time at the injury sites, hyaluronic acid was derivatized with dopamine, and a novel cross-linking mechanism was suggested. To optimize drug release profile, atorvastatin was encapsulated into biodegradable polymer by spray-drying. The microspheres showed activity towards synthetic vascular smooth muscle cells in vitro. The device showed a burst release phase to target IH in the hyper-acute stage, followed by a sustained release to supply the drug continuously over several weeks, and demonstrated biocompatibility in vivo.

Keywords
  • Intimal hyperplasia
  • Atorvastatin
  • Hyaluronic acid
  • Bioadhesion
  • Spray-drying
  • PLGA
  • Vascular smooth muscle cells
Citation (ISO format)
MELNIK, Tamara. Controlled drug delivery systems for perivascular application and intimal hyperplasia prevention. Doctoral Thesis, 2022. doi: 10.13097/archive-ouverte/unige:165764
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Creation12/19/2022 9:34:00 AM
First validation12/19/2022 9:34:00 AM
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Status update03/16/2023 10:14:26 AM
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