Perivascular sustained release of atorvastatin from a hydrogel-microparticle delivery system decreases intimal hyperplasia.

Détails

ID Serval
serval:BIB_2C420201E7CB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Perivascular sustained release of atorvastatin from a hydrogel-microparticle delivery system decreases intimal hyperplasia.
Périodique
Journal of controlled release
Auteur(s)
Mylonaki I., Strano F., Deglise S., Allémann E., Alonso F., Corpataux J.M., Dubuis C., Haefliger J.A., Jordan O., Saucy F., Delie F.
ISSN
1873-4995 (Electronic)
ISSN-L
0168-3659
Statut éditorial
Publié
Date de publication
28/06/2016
Peer-reviewed
Oui
Volume
232
Pages
93-102
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Intimal hyperplasia (IH) is the major cause of grafted vessel occlusion and occurs frequently after bypass intervention. No pharmaceutical formulation is currently available to prevent this pathology. Local perivascular delivery of an appropriate active compound released in a time-dependent manner (from day one up to 4weeks) is necessary for an efficient single-administration preventive therapy. To this aim, we propose the combination of gel and microparticles delivery system containing atorvastatin (ATV). The incorporation of ATV in a cross-linked hyaluronic acid gel, provided in vitro a fast release over 3days, while ATV-loaded poly-lactic-co-glycolic acid (PLGA) microparticles dispersed in the gel gave a sustained release over 4weeks. In vivo, ATV formulations were applied perivascularly in mice undergoing carotid artery ligation. IH was significantly reduced (-68%) in presence of ATV incorporated in hyaluronic acid gel and encapsulated in microparticles compared to control. No significant IH alteration was observed when ATV was incorporated only in the gel (fast release) or only in the microparticles (slow release) demonstrating that a biphasic release of ATV is essential to interfere with the development of IH. ATV was detected in adjacent tissues 28days after the intervention, showing the sustained presence of the drug in vivo. After four weeks ATV was not detected in remote tissues, except at a very low concentration (0.044ng/mg) in the liver, suggesting a very low risk of systemic toxicity of locally delivered ATV. Additionally, the ex vivo data showed that ATV in solution permeates through isolated human saphenous veins and thus is a good candidate for perivascular delivery. Our data demonstrate that a local biphasic ATV release on the mice ligated carotid efficiently prevents the development of IH without apparent toxicity.

Mots-clé
Animals, Atorvastatin Calcium/administration & dosage, Atorvastatin Calcium/pharmacokinetics, Atorvastatin Calcium/therapeutic use, Carotid Arteries/pathology, Carotid Arteries/surgery, Delayed-Action Preparations/administration & dosage, Delayed-Action Preparations/pharmacokinetics, Delayed-Action Preparations/therapeutic use, Drug Delivery Systems, Drug Liberation, Humans, Hyaluronic Acid/administration & dosage, Hyaluronic Acid/pharmacokinetics, Hyaluronic Acid/therapeutic use, Hydrogels/administration & dosage, Hydrogels/pharmacokinetics, Hydrogels/therapeutic use, Hyperplasia/drug therapy, In Vitro Techniques, Lactic Acid/administration & dosage, Lactic Acid/pharmacokinetics, Lactic Acid/therapeutic use, Ligation, Male, Mice, Inbred C57BL, Polyglycolic Acid/administration & dosage, Polyglycolic Acid/pharmacokinetics, Polyglycolic Acid/therapeutic use, Saphenous Vein/metabolism, Tissue Distribution, Tunica Intima/pathology, Atorvastatin, Hyaluronic acid hydrogel, Intimal hyperplasia, Microparticle, Perivascular administration
Pubmed
Web of science
Création de la notice
03/05/2016 17:39
Dernière modification de la notice
20/08/2019 14:11
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