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

Mylonaki, Ioanna; Strano, Francesco; Déglise, Sebastien; Allémann, Éric; Alonso, Florian; Corpataux, Jean-Marc; Dubuis, Céline; Haefliger, Jacques‐Antoine; Jordan, Olivier; Saucy, François; Delié, Florence

doi:10.1016/j.jconrel.2016.04.023

Cited by 31 publications

(42 citation statements)

References 52 publications

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“…Delie and coworkers developed an easily applicable drug delivery system for the prevention of intimal hyperplasia, through a single administration of a cross‐linked hyaluronic acid hydrogel/poly‐lactic‐co‐glycolic acid (PLGA) microparticle formulation loaded with atorvastatin. Theirs in vivo studies showed that the combination of a fast and sustained release of atorvastatin provided a synergistic effect, which efficiently inhibited the development of intimal hyperplasia . Ma and coworkers synthesized injectable composite hydrogels composed of alginate microspheres and PLGA–PEG–PLGA hydrogel as a double barrier system to greatly suppress the burst release and to prolong the release time of water‐soluble drugs .…”

Section: Introductionmentioning

confidence: 99%

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

Karamzadeh

Asl

Rahmani

2020

J of Applied Polymer Sci

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Hydrogels have increasingly received considerable attention for local opioids delivery in order to sustained wound pain relief. However, burst release of drugs is a critical problem of hydrogels. To this aim, a local drug delivery system consisting of polycaprolactone (PCL) microspheres containing methadone hydrochloride/polyethylene glycol (PEG)-based hydrogels were developed to prolong drug release with potential utilization in pain treatment. Four different drug delivery systems, including methadone hydrochloride/PEG-(N 3 ) 4 -based hydrogel, methadone hydrochloride/PEG-(N 3 ) 2 -based hydrogel, methadone hydrochloride/PCL/PEG-(N 3 ) 4 , and methadone hydrochloride/PCL/PEG-(N 3 ) 2 composite hydrogels, were fabricated to investigate drug release profiles of these systems. The results showed that drug released can be controlled by both the double-barrier matrix (hydrogel/microsphere), and the crosslinking density of hydrogels. Therefore, methadone hydrochloride/PCL/PEG-(N 3 ) 2 composite hydrogel with high crosslinking density has great potential application in sustained release systems for wound pain relief.

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Section: Introductionmentioning

confidence: 99%

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

Karamzadeh

Asl

Rahmani

2020

J of Applied Polymer Sci

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“…This formulation was shown to reduce IH by 68% at 4 weeks in a mouse carotid artery ligation model. 13 …”

Section: Discussionmentioning

confidence: 99%

“…This paradigm for prolonging drug efficacy was further supported by a recent report in which combining PLGA microparticles (15 μ m in diameter) with a cross-linked hyaluronic acid gel markedly extended drug release and inhibition of IH in a mouse model for 4 weeks. 13 These studies indicate that prolonged drug release produces durable efficacy. Thus, a perivascular delivery system capable of long-term drug release is highly desirable for developing effective treatments for IH.…”

Section: Introductionmentioning

confidence: 96%

Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats

et al. 2017

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At present, there are no clinical options for preventing neointima-caused (re)stenosis after open surgery such as bypass surgery for treating flow-limiting vascular disease. Perivascular drug delivery is a promising strategy, but in translational research, it remains a major challenge to achieve long-term (e.g., > 3 months) anti(re)stenotic efficacy. In this study, we engineered a unique drug delivery system consisting of durable unimolecular micelles, formed by single multiarm star amphiphilic block copolymers with only covalent bonds, and a thermosensitive hydrogel formed by a poly(lactide-co-glycolide)–poly(ethylene glycol)–poly(lactide-co-glycolide) triblock copolymer (abbreviated as triblock gel) that is stable for about 4 weeks in vitro. The drug-containing unimolecular micelles (UMs) suspended in Triblock gel were able to sustain rapamycin release for over 4 months. Remarkably, even 3 months after perivascular application of the rapamycin-loaded micelles in Triblock gel in the rat model, the intimal/medial area ratio (a restenosis measure) was still 80% inhibited compared to the control treated with empty micelle/gel (no drug). This could not be achieved by applying rapamycin in Triblock gel alone, which reduced the intimal/medial ratio only by 27%. In summary, we created a new UM/Triblock gel hybrid system for perivascular drug delivery, which produced a rare feat of 3-month restenosis inhibition in animal tests. This system exhibits a real potential for further translation into an anti(re)stenotic application with open surgery.

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“…These systems should have adequate mechanical properties in order to be bent, sutured or injected and to remain on site for the desired period of time. Semi-solids, most frequently gels, present the advantages of easy handling and conformable covering of the graft [66]. Indeed, a gel should be easily manipulated by the surgeon to cover the anastomosis as well as the graft itself ( Fig.…”

Section: Properties Of Perivascular Systemsmentioning

confidence: 99%

Perivascular medical devices and drug delivery systems: Making the right choices

et al. 2017

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Perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery. These systems provide mechanical support and/or pharmacological activity for the prevention of intimal hyperplasia following vessel injury. Despite abundant reports in the literature and numerous clinical trials, no efficient perivascular treatment is available. In this review, the existing perivascular medical devices and perivascular drug delivery systems, such as polymeric gels, meshes, sheaths, wraps, matrices, and metal meshes, are jointly evaluated. The key criteria for the design of an ideal perivascular system are identified. Perivascular treatments should have mechanical specifications that ensure system localization, prolonged retention and adequate vascular constriction. From the data gathered, it appears that a drug is necessary to increase the efficacy of these systems. As such, the release kinetics of pharmacological agents should match the development of the pathology. A successful perivascular system must combine these optimized pharmacological and mechanical properties to be efficient.

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

Cited by 31 publications

References 52 publications

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats

Perivascular medical devices and drug delivery systems: Making the right choices

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