Targeted Nanotherapeutic Nucleotide Delivery For Preventing Arteriovenous Fistula Failure
SUMMARY
- Surgically created arteriovenous fistula (AVF) is the preferred vascular access means for treating terminal renal failure through hemodialysis. 60% of AVF’s fail as effective dialysis points due to vascular stenosis.
- This disturbed blood flow stimulates vascular inflammation by increasing the expression of vascular cell adhesion molecule 1 (VCAM-1) and microRNA-92a (miR-92a) in endothelial cells leading to vascular and inflammation disorders.
- Peptide-targeted polyelectrolyte complex micelles designed to administer nanotherapeutics to vascular cells have been shown to reduce AVF failure incidence. Polyelectrolyte complex micelles ensheathed by biocompatible polymers deliver therapeutic nucleotides to AVF-involved cells, while shielding them from degradation by serum nuclease, renal clearance, and immunogenic response.
- The faculty inventors has developed nanoparticles that target inflamed endothelial cells (by targeting VCAM-1 expression) to deliver miR-92a inhibitors to reduce AVF failure and stenosis. Cell-targeting peptides peripheral to the micelles promote cell-specific delivery, while reducing cytotoxicity and prolonging circulation by preventing nonspecific serum interactions.
FIGURE
ADVANTAGES
ADVANTAGES
- High stability against renal clearance, immunologic response and degradation by serum nuclease
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Low cytotoxicity and enhanced circulation and safety
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High cellular and receptor specificity
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High scalability due to complete automation of micelle synthesis and facile modification of the cell-targeting peptides.
APPLICATIONS
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Treating and preventing AVF failure
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Out-patient angioplasty and stent placement procedures
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Broadly applicable, safe, and effective intravenous nanotherapeutics delivery system