Controlled Delivery of Rosuvastatin or Rapamycin through Electrospun Bismuth Nanoparticle-Infused Perivascular Wraps Promotes Arteriovenous Fistula Maturation

Authors

Allan John R Barcena
Joy Vanessa D Perez
Marvin R Bernardino
Erin Marie D San Valentin
Jossana A Damasco
Carleigh Klusman
Benjamin Martin
Karem A Court
Biana Godin
Gino Canlas
Natalie Fowlkes
Richard R Bouchard
Jizhong Cheng
Steven Y Huang
Marites P Melancon

Publication Date

7-3-2024

Journal

ACS Applied Materials & Interfaces

DOI

10.1021/acsami.4c06042

PMID

38912610

PMCID

PMC11725229

PubMedCentral® Posted Date

7-3-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

In the context of arteriovenous fistula (AVF) failure, local delivery enables the release of higher concentrations of drugs that can suppress neointimal hyperplasia (NIH) while reducing systemic adverse effects. However, the radiolucency of polymeric delivery systems hinders long-term in vivo surveillance of safety and efficacy. We hypothesize that using a radiopaque perivascular wrap to deliver anti-NIH drugs could enhance AVF maturation. Through electrospinning, we fabricated multifunctional perivascular polycaprolactone (PCL) wraps loaded with bismuth nanoparticles (BiNPs) for enhanced radiologic visibility and drugs that can attenuate NIH—rosuvastatin (Rosu) and rapamycin (Rapa). The following groups were tested onto the AVFs of a total of 24 Sprague-Dawley rats with induced chronic kidney disease: control (i.e., without wrap), PCL-Bi (i.e., wrap with BiNPs), PCL-Bi-Rosu, and PCL-Bi-Rapa. We found that BiNPs significantly improved the wraps’ radiopacity without affecting biocompatibility. The drug release profiles of Rosu (hydrophilic drug) and Rapa (hydrophobic drug) differed significantly. Rosu demonstrated a burst release followed by gradual tapering over 8 weeks, while Rapa demonstrated a gradual release similar to that of the hydrophobic BiNPs. In vivo investigations revealed that both drug-loaded wraps can reduce vascular stenosis on ultrasonography and histomorphometry as well as reduce [18F]Fluorodeoxyglucose uptake on positron emission tomography. Immunohistochemical studies revealed that PCL-Bi-Rosu primarily attenuated endothelial dysfunction and hypoxia in the neointimal layer, while PCL-Bi-Rapa modulated hypoxia, inflammation, and cellular proliferation across the whole outflow vein. In summary, the controlled delivery of drugs with different properties and mechanisms of action against NIH through a multifunctional, radiopaque perivascular wrap can improve imaging and histologic parameters of AVF maturation.

Keywords

Animals, Rats, Sprague-Dawley, Rats, Sirolimus, Rosuvastatin Calcium, Bismuth, Polyesters, Male, Arteriovenous Fistula, Metal Nanoparticles, Neointima, Nanoparticles, Humans, Drug Liberation, chronic kidney disease, drug delivery systems, electrospinning, nanocomposite, neointimal hyperplasia, radiopacity, vascular remodeling

Published Open-Access

yes

Recommended Citation

Barcena, Allan John R; Perez, Joy Vanessa D; Bernardino, Marvin R; et al., "Controlled Delivery of Rosuvastatin or Rapamycin through Electrospun Bismuth Nanoparticle-Infused Perivascular Wraps Promotes Arteriovenous Fistula Maturation" (2024). Faculty, Staff and Student Publications. 4254.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4254