nano & microparticle drug delivery: how will it play a role in peripheral arterial interventions
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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. - PowerPoint PPT PresentationTRANSCRIPT
Nano & Microparticle Drug Delivery:
How will it play a role in peripheral arterial interventions
Subhash Banerjee, MDAssociate Prof. of MedicineUT 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-Coated Balloon Manufacturer Drug Carrier Drug Dose Density (µg/mm²)
Cotavance MEDRAD Paccocath Paclitaxel 3
SeQuent Please B. Braun Melsungen AG Paccocath Paclitaxel 3
IN. PACT Medtronic-Invatec FreePac Paclitaxel 3.5
Dior, Freeway Eurocor Shellac Paclitaxel 3
Moxy Lutonix-Bard Nonpolymeric Paclitaxel 2
Pantera Lux Biotronik Butyryl-tri-hexyl citrate Paclitaxel 3
AngioSculpt AngioScore unkonwn Paclitaxel 3
Protege Blue Medical unknown Paclitaxel 3
Elutax Aachen Resonance No (2 layers of paclitaxel) Paclitaxel 2
Wombat Avidal Vascular No (paclitaxel wrapped) Paclitaxel 3.3
Magic Touch Concept Medical Phospholipid based excipient Sirolimus 1.2
Drug Concentration of Current DCB
Waxman et al. JACC Cardiovasc Interv.2012; 5:1001-12
DCB 6x60 mm; 1 inflation=3391µgPaclitaxel 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
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. 2013 Aug;6(4):570-8
MLNP Uptake by Injured Endothelial Cells (EC)
Banerjee et al. J Cardiovasc Transl Res. 2013 Aug;6(4):570-8
PLGA-PEG PLGA-PEG-Gp1b PLGA-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. 2012 Aug;5(4):519-27
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
Paclitaxelsolution
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)
Rat Carotid Balloon Injury Model
IN. PACT
Wombat
Cotavance
SeQuent Please
Dior, Freeway
Pantera Lux
AngioSculpt Scoring
Protege
Moxy
Elutax
Magic Touch
Nanoparticle incorporated
0 0.5 1 1.5 2 2.5 3 3.5 4
3.5
3.3
3
3
3
3
3
3
2
2
1.2
0.4
Drug dosage density on balloon (mcg/mm2)
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