A biodegradable perivascular wrap for controlled, local and directed drug delivery

Area of Science:

• Biomaterials Science
• Vascular Surgery
• Pharmacology

Background:

• Hyperplasia of synthetic vascular grafts, particularly arteriovenous (AV) grafts for hemodialysis, leads to stenosis.
• Current perivascular drug delivery systems often release agents to both target and non-target tissues, reducing efficacy and increasing side effects.

Purpose of the Study:

• To develop a biodegradable, perivascular delivery system for localized, sustained, and unidirectional drug release.
• To inhibit hyperplasia in synthetic AV grafts used for chronic hemodialysis.

Main Methods:

• Fabrication of polymer bilayer wraps using polylactide-co-glycolide (PLGA) or polycaprolactone (PCL) with a non-porous barrier layer.
• Loading of sunitinib (a tyrosine kinase inhibitor) into either a non-porous or porous layer, or infused hydrogel.
• In vitro drug release assays and degradation studies.
• In vivo pharmacokinetic assessment in a porcine model.

Main Results:

• The non-porous polylactide-co-glycolide (PLGA) barrier layer demonstrated superior performance in inhibiting drug diffusion compared to polycaprolactone (PCL).
• Drug release duration was significantly prolonged with non-porous constructs (PLGA: 9 days, PCL: 22 days) compared to porous constructs (PLGA: 3 days, PCL: 5 days).
• In vivo studies showed minimal extravascular drug levels at 1 and 4 weeks, with high concentrations retained in the target vein segment, confirming effective localized delivery.

Conclusions:

• The developed PLGA-based perivascular bilayer wrap effectively achieves localized and sustained drug delivery, minimizing extravascular diffusion.
• This system shows significant promise for treating hemodialysis AV graft hyperplasia and potentially other vascular hyperplastic disorders.
• The construct's mechanical properties, including stiffening with hydration, may offer beneficial resistance to venous stress in AV grafting.