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Nano & Microparticle Drug Delivery: How will it play a role in peripheral arterial interventions

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.

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Nano & Microparticle Drug Delivery: How will it play a role in peripheral arterial interventions

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  1. Nano&MicroparticleDrug Delivery:How will it play a role in peripheral arterial interventions SubhashBanerjee, MD Associate Prof. of Medicine UT Southwestern Med. Ctr. Nov. 2013

  2. 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. ThrombHaemost. 2009; 101: 201–206

  3. Drug Concentration of Current DCB DCB 6x60 mm; 1 inflation=3391µg 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: 2289-2295 Waxman et al. JACC Cardiovasc Interv.2012; 5:1001-12

  4. Multi-LigandNanoparticles (MLNP) • “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 Paclitaxel Banerjee et al. J CardiovascTransl Res. 2013 Aug;6(4):570-8

  5. MLNP Uptake by Injured Endothelial Cells (EC) Under flow conditions EC delivery PLGA-PEG PLGA-PEG-Gp1b PLGA-PEG-Gp1b/TAT Banerjee et al. J CardiovascTransl Res. 2013 Aug;6(4):570-8

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

  7. Transfer of MLNP Coated Angioplasty Balloon to Rat Artery Angioplasty balloon without coating of nanoparticles Angioplasty balloon coated with nanoparticles before inflation Angioplasty balloon coated with nanoparticles after inflation-deflation Rat carotid artery before angioplasty Rat carotid artery after angioplasty 27% particles were lost 7% particles were transferred to the artery wall Banerjee et al. J CardiovascTransl Res. 2012 Aug;5(4):519-27

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

  9. Paciltaxel-Loaded MLNP Suppresses Rat Carotid Artery Neointima Rat Carotid Balloon Injury Model Banerjee et al. J CardiovascTransl Res. (in submission)

  10. Drug Concentration of DCB

  11. 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

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