Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challeng...

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Bibliographic Details
Published in:International journal of molecular sciences Vol. 23; no. 10; p. 5706
Main Authors: Melnik, Tamara, Ben Ameur, Senda, Kanfar, Nasreddine, Vinet, Laurent, Delie, Florence, Jordan, Olivier
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 20-05-2022
MDPI
Subjects:
Adhesion
Adhesives
Atorvastatin
bioadhesion
Biocompatibility
Biodegradability
Caustic soda
Coronary vessels
Crosslinking
Cytotoxicity
Dopamine
Drug delivery
Drug delivery systems
Fibroblasts
Hyaluronic acid
hydrogel
Hydrogels
Hyperplasia
initiator-free crosslinking
Initiators
mussel inspired polymers
Oxidation resistance
Oxidizing agents
perivascular administration
Rheological properties
Rheology
Sodium
Spectrum analysis
Surgery
Thickening
Toxicity
Vascular tissue
mussel inspired polymers
hydrogel
initiator-free crosslinking
bioadhesion
atorvastatin
perivascular administration
hyaluronic acid
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Summary:Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23105706