Bioadhesive Perivascular Microparticle-Gel Drug Delivery System for Intimal Hyperplasia Prevention: In Vitro...

Area of Science:

• Biomaterials Science
• Vascular Surgery
• Pharmacology

Background:

• Intimal hyperplasia (IH) is a major cause of graft failure after bypass surgery, driven by vascular smooth muscle cell proliferation.
• Current treatments lack effective long-term perivascular drug delivery to prevent IH.
• Atorvastatin (ATV) shows potential but requires a suitable delivery system for sustained local action.

Purpose of the Study:

• To develop and characterize a novel bioadhesive drug delivery system for topical perivascular application of atorvastatin (ATV).
• To achieve sustained release of ATV over 5-8 weeks to coincide with IH progression.
• To evaluate the system's bioadhesion, rheological properties, and biocompatibility for preventing intimal hyperplasia.

Main Methods:

• Encapsulation of ATV in a two-component system: hyaluronic acid-dopamine (HA-DOPA) bioadhesive gel and biodegradable microparticles.
• Characterization using scanning electron microscopy, rheology, in vitro release studies, and bioadhesion tests on porcine arteries.
• Preliminary subcutaneous biocompatibility assessment in rats.

Main Results:

• The HA-DOPA gel exhibited suitable rheological properties for perivascular application.
• Demonstrated superior bioadhesion and cohesion compared to control HA formulations.
• Achieved an initial burst release of ATV followed by sustained release over 8 weeks.
• Preliminary studies showed good subcutaneous biocompatibility in rats.

Conclusions:

• The developed HA-DOPA microparticle system provides an effective dual-release drug delivery platform for perivascular ATV application.
• This system shows significant potential for preventing intimal hyperplasia and improving graft patency in vascular surgery.
• Offers a promising new strategy for localized, long-term treatment to combat graft failure.