1. 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

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. Thromb Haemost. 2009; 101: 201–206

3. Drug Concentration of Current DCB
Drug-Coated Balloon
Manufacturer
Drug Carrier
Drug
Dose Density (µg/mm²)
Cotavance
MEDRAD
Paccocath
Paclitaxel 3
SeQuent Please
B. Braun Melsungen AG
IN. PACT
Medtronic-Invatec
FreePac
3.5
Dior, Freeway
Eurocor
Shellac
Moxy
Lutonix-Bard
Nonpolymeric 2
Pantera Lux
Biotronik
Butyryl-tri-hexyl citrate
AngioSculpt
AngioScore
unkonwn
Protege
Blue Medical
unknown
Elutax
Aachen Resonance
No (2 layers of paclitaxel)
Wombat
Avidal Vascular
No (paclitaxel wrapped)
3.3
Magic Touch
Concept Medical
Phospholipid based excipient
Sirolimus
1.2
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:
Increased dose
Balloon surface modifications that increase surface area and retention (contrast, fatty acids, urea)
Paclitaxel: binding to the β subunit of tubulin, resulting in arrest of microtubule function. Paclitaxel is also characterized by prolonged tissue retention rates
sq mm; 3391 microgm; microgm
Waxman et al. JACC Cardiovasc Interv.2012; 5:

4. 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

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 Cardiovasc Transl Res 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
Xu Hao 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 Cardiovasc Transl Res Aug;5(4):519-27

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

9. Paciltaxel-Loaded MLNP Suppresses Rat Carotid Artery Neointima
Rat Carotid Balloon Injury Model
Banerjee et al. J Cardiovasc Transl 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