Nano & Microparticle Drug Delivery: How will it play a role in peripheral arterial interventions Subhash Banerjee, MD Associate Prof. of Medicine UT Southwestern Med. Ctr. Nov. 2013

Drug Coated Balloon (DCB) for Peripheral Arterial Interventions  Success of DCB relies on the rapid transfer of a single dose of an anti-proliferative agent into the vessel wall  The dominant challenge for DCB is rapid, uniform, efficient, & directed transfer of the drug to the vessel wall during balloon inflation with limited downstream distribution  Tissue delivery=8.8±3.9% of the mean percentage of total original catheter load Cremers et al. Thromb Haemost. 2009; 101: 201–206

Drug Concentration of Current DCB Waxman et al. JACC Cardiovasc Interv.2012; 5: DCB 6x60 mm; 1 inflation=3391 µg Paclitaxel coated balloon= Low-dose (0.2 μg/stent) Intermediate-dose (15 μg/stent) High-dose (187 μg/stent) Heldman et al. Circulation. 2001; 103: DCB 6x60 mm; 1 inflation=3391 µg Paclitaxel coated balloon= Low-dose (0.2 μg/stent) Intermediate-dose (15 μg/stent) High-dose (187 μg/stent) Heldman et al. Circulation. 2001; 103:

Multi-Ligand Nanoparticles (MLNP) Paclitaxel  “Platelet mimicking”  Poly (L-lactic-co-glycolic acid) (PLGA)  Surface conjugated ligands:  polyethylene glycol (PEG)  glycoprotein 1b (GP1b)  trans-activating transcriptional peptide (TAT)  Extensive biocompatibility testing Banerjee et al. J Cardiovasc Transl Res Aug;6(4):570-8

MLNP Uptake by Injured Endothelial Cells (EC) Banerjee et al. J Cardiovasc Transl Res Aug;6(4):570-8 PLGA-PEGPLGA-PEG-Gp1bPLGA-PEG-Gp1b/TAT Under flow conditions EC delivery

Drug Delivering MLNP Coated Balloon Xu Hao et al. TCT 2013 Fluorescent Image of Nanoparticle- coated Angioplasty Balloon Tip Nanoparticle-coated balloon surface after inflation/deflation Uncoated angioplasty balloon surface Nanoparticle-coated balloon surface before inflation Surface SEM of Nanoparticle- coated Angioplasty Balloon

Transfer of MLNP Coated Angioplasty Balloon to Rat Artery Banerjee et al. J Cardiovasc Transl Res Aug;5(4): A.Angioplasty balloon without coating of nanoparticles B.Angioplasty balloon coated with nanoparticles before inflation C.Angioplasty balloon coated with nanoparticles after inflation-deflation D.Rat carotid artery before angioplasty E.Rat carotid artery after angioplasty 7% particles were transferred to the artery wall 27% particles were lost

Paciltaxel-Loaded MLNP Suppresses Rat Carotid Artery Neointima Banerjee et al. J Cardiovasc Transl Res. (in submission) Uninjured Normal saline Nanoparticles w/o paclitaxel Paclitaxel solution Paclitaxel- loaded nanoparticle Rat Carotid Balloon Injury Model

Paciltaxel-Loaded MLNP Suppresses Rat Carotid Artery Neointima Banerjee et al. J Cardiovasc Transl Res. (in submission)

Drug Concentration of DCB

MLNP Loaded DCB for Peripheral Arterial Interventions  Paclitaxel containing biodegradable, MLNP can be loaded on angioplasty balloons & delivered reliably to injured vascular surfaces with demonstrable suppression of neointimal proliferation  MLNP-DCB may potentially offer a pathway for targeted drug delivery to injured vascular wall, at significantly reduced doses  Future studies to refine the technology, assess comparative efficacy & safety are on-going