Formulation and delivery mode affect disposition and activity of tyrphostin-loaded nanoparticles in the rat carotid model

Ilia Fishbein, Michael Chorny, Shmuel Banai, Alexander Levitzki, Haim D. Danenberg, Jianchuan Gao, Xing Chen, Evgeny Moerman, Irith Gati, Victoria Goldwasser, Gershon Golomb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Poor drug residence in the arterial wall hinders clinical implementation of local drug delivery strategies for the treatment of restenosis. A rat carotid model of vascular injury and intraluminal delivery of tyrphostin-containing polylactic acid (PLA) nanoparticles (NPs) were used to determine the relationship between residence properties and biological activity of different formulations and administration modes. The effects of delivery modes (denudation and delivery time) and formulation variables (adsorbed vs encapsulated drug, and NP size) on arterial drug/NP retention were examined. Antirestenotic effects of large (160 nm) and small (90 nm) tyrphostin-containing NPs, surface-absorbed tyrphostin, and systemic treatment were compared. Fluorescent NPs were used to study the spatial distribution of the carrier in the arterial wall. The decrease in arterial tyrphostin level over time fitted a biexponential model. Delivery time and pressure, endothelium integrity, particle size, and drug-polymer association affected local pharmacokinetics and the antirestenotic results after 14 days. The PLA-based tyrphostin NP formulation ensured a prolonged drug residence at the angioplasty site after single intraluminal application. Several readily adjustable formulation and procedural factors considerably modified arterial ingress of the drug-loaded NPs and governed their subsequent redistribution, tissue binding, elimination, and ensuing antirestenotic effect.

Original languageEnglish
Pages (from-to)1434-1439
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
StatePublished - 2001
Externally publishedYes


  • Controlled release
  • Local delivery
  • Nanoparticles
  • Restenosis
  • Tyrphostins


Dive into the research topics of 'Formulation and delivery mode affect disposition and activity of tyrphostin-loaded nanoparticles in the rat carotid model'. Together they form a unique fingerprint.

Cite this