title: Targeted biodegradable nanoparticles for drug delivery to smooth muscle cells.
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,L-lactic-co-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 peptide-conjugated 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.
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Soujanya
authors.initials: S
authors.lastname: Kona
authors.forename: Danyel
authors.initials: D
authors.lastname: Specht
authors.forename: Maham
authors.initials: M
authors.lastname: Rahimi
authors.forename: Bhavik P
authors.initials: BP
authors.lastname: Shah
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Gilbertson
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D020341:Absorbable Implants; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D010982:Platelet-Derived Growth Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid