Delivery of N-Cadherin Targeting Peptides to Vascular Tissues by Surface-Modified Polyurethane Nanoparticles via a Drug-Coated Balloon.

Restenosis remains a long-standing limitation to effectively maintain functional blood flow after percutaneous transluminal angioplasty (PTA). While the use of drug-coated balloons (DCBs) containing antiproliferative drugs has improved patient outcomes, limited tissue transfer and poor therapeutic targeting capabilities contribute to off-target cytotoxicity, precluding adequate endothelial repair. In this work, a DCB system was designed and tested to achieve defined arterial delivery of an antirestenosis therapeutic candidate, cadherin-2 (N-cadherin) mimetic peptides (NCad), shown to selectively inhibit smooth muscle cell migration and limit intimal thickening in early animal PTA models.

Synthesis, characterization, and surface modification of degradable polar hydrophobic ionic polyurethane nanoparticles for the delivery of therapeutics to vascular tissue.

Degradable polar hydrophobic ionic polyurethanes (D-PHI) are an emerging class of biomaterials with particular significance for blood-contacting applications due to their immunomodulatory effects and highly customizable block chemistry. In this manuscript, D-PHI polymer was formulated as a nanoparticle excipient for the first time by inverse emulsion polymerization. The nanoparticles were optimized with consideration of diameter, surface charge, size variability, and yield as a delivery vehicle for a custom vascular therapeutic peptide.

Matrix-Binding, N-Cadherin-Targeting Chimeric Peptide Inhibits Intimal Thickening but Not Endothelial Repair in Balloon-Injured Carotid Arteries.

Background: Treatment of occluded vessels can involve angioplasty, stenting, and bypass grafting, which can be limited by restenosis and thrombosis. Drug-eluting stents attenuate restenosis, but the current drugs used are cytotoxic, causing smooth muscle cell (SMC) and endothelial cell (EC) death that may lead to late thrombosis. N-cadherin is a junctional protein expressed by SMCs, which promotes directional SMC migration contributing to restenosis.

Heart Rate Variability Responses of Individuals With and Without Saline-Induced Obstructive Sleep Apnea.

Study Objectives: Postoperative development of obstructive sleep apnea (OSA) has been attributed to the fluid overloaded state of patients during the postoperative period. In this context, alterations in cardiac autonomic regulation caused by OSA may explain the increased postoperative risk for adverse cardiovascular events. This study tests the hypothesis that individuals with fluid overload-induced OSA will experience autonomic dysregulation, compared to those without fluid overload-induced OSA.

The Effect of Electrical Stimulation of the Calf Muscle on Leg Fluid Accumulation over a Long Period of Sitting.

Leg fluid accumulation during sedentary behaviours such as sitting can lead to leg edema and associated adverse health consequences. This study investigates the use calf muscle electrical stimulation (ES) to reduce seated leg fluid accumulation. Thirteen non-obese, normotensive men (mean age 51 yr.

Leg fluid accumulation during prolonged sitting.

The accumulation of fluid in the legs due to sedentariness can be a health risk in extreme cases. Negative health impacts associated with leg fluid accumulation include leg edema and risk of blood clots. Furthermore, fluid accumulating in the legs is accompanied by fluid shift into the upper body which is also associated with health risks such as: increased blood pressure when lying down, respiratory problems in people with heart failure, and increased sleep apnea.