Targeted biodegradable nanoparticles for drug delivery to smooth muscle cells

Soujanya Kona, Danyel Specht, Maham Rahimi, Bhavik P. Shah, Timothy A. Gilbertson, Kytai T. Nguyen

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Targeted delivery of therapeutic agents to prevent smooth muscle cell (SMC) proliferation is important in averting restenosis (a narrowing of blood vessels). Since platelet derived growth factor (PDGF) receptors are over-expressed in proliferating SMCs after injury from cardiovascular interventions, such as angioplasty and stent implantation, our hypothesis is that conjugation of PDGF-BB (platelet-derived growth factor BB (homodimer)) peptides to biodegradable poly (D,Llacticco-glycolide) (PLGA) nanoparticles (NPs) would exhibit an increased uptake of these NPs by proliferating SMCs. In this study, poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles containing dexamethasone were formulated and conjugated with PDGF-BB peptides. These NPs were stable, biocompatible, and exhibited a sustained drug release over 14 days. Various particle uptake studies using HASMCs (human aortic smooth muscle cells) demonstrated that PDGF-BB peptideconjugated nanoparticles significantly increased cellular uptake and decreased proliferation of HASMCs compared to control nanoparticles (without conjugation of PDGF-BB peptides). These NPs were internalized primarily by clathrin-mediated endocytosis and macropinocytosis. Our in vitro results suggest that PDGF-BB peptide-conjugated NPs could represent as an effective targeted, sustained therapeutic delivery system to reduce restenosis and neointimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)236-244
Number of pages9
JournalJournal of Nanoscience and Nanotechnology
Volume12
Issue number1
DOIs
StatePublished - 2012

Keywords

  • Anti-proliferation
  • Biodegradable nanoparticles
  • Human aortic smooth muscle cells
  • Platelet-derived growth factor
  • Targeted drug delivery

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics

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