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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

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

drug coated balloon dcb for peripheral arterial interventions
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

slide3

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

multi ligand nanoparticles mlnp
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

mlnp uptake by injured endothelial cells ec
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

drug delivering mlnp coated balloon
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

transfer of mlnp coated angioplasty balloon to rat artery
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

paciltaxel loaded mlnp suppresses rat carotid artery neointima
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)

paciltaxel loaded mlnp suppresses rat carotid artery neointima1
Paciltaxel-Loaded MLNP Suppresses Rat Carotid Artery Neointima

Rat Carotid Balloon Injury Model

Banerjee et al. J CardiovascTransl Res. (in submission)

mlnp loaded dcb for peripheral arterial interventions
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