Drug-coated Nanoparticles

Report
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
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
DCBPaclitaxel
6x60 mm; 1 inflation=3391µg
3
Protege
Blue Medical
unknown
Paclitaxel
coated balloon=
Paclitaxel
3
Elutax
Aachen Resonance
Wombat
Avidal Vascular
Magic Touch
Concept Medical
Low-dose (0.2 μg/stent)
No (2 layers of
Paclitaxel
2
paclitaxel)
Intermediate-dose (15 μg/stent)
No (paclitaxel
Paclitaxel
3.3
wrapped)
High-dose (187 μg/stent)
Phospholipid
Heldman
et al. Circulation. 2001;
Sirolimus
1.2 103: 2289-2295
based excipient
Waxman et al. JACC Cardiovasc Interv.2012; 5:1001-12
Multi-Ligand Nanoparticles
(MLNP)
 “Platelet mimicking”
Paclitaxel
 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)
Under flow conditions
EC delivery
PLGA-PEG
PLGA-PEG-Gp1b
PLGA-PEG-Gp1b/TAT
Banerjee et al. J Cardiovasc Transl Res. 2013 Aug;6(4):570-8
Drug Delivering MLNP Coated
Balloon
Fluorescent Image of Nanoparticlecoated Angioplasty Balloon Tip
Surface SEM of Nanoparticlecoated 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
Transfer of MLNP Coated
Angioplasty Balloon to Rat Artery
A. Angioplasty balloon without
coating of nanoparticles
B. Angioplasty balloon coated
with nanoparticles before
inflation
C. Angioplasty balloon coated
with nanoparticles after
inflation-deflation
27% particles
were lost
7% particles
were transferred
to the artery wall
D. Rat carotid artery before
angioplasty
E. Rat carotid artery after
angioplasty
Banerjee et al. J Cardiovasc Transl Res. 2012 Aug;5(4):519-27
Paciltaxel-Loaded MLNP Suppresses
Rat Carotid Artery Neointima
Rat Carotid Balloon Injury Model
Uninjured
Normal saline
Nanoparticles
w/o paclitaxel
Paclitaxel
solution
Paclitaxelloaded
nanoparticle
Banerjee et al. J Cardiovasc Transl Res. (in submission)
Paciltaxel-Loaded MLNP Suppresses
Rat Carotid Artery Neointima
Rat Carotid Balloon Injury Model
Banerjee et al. J Cardiovasc Transl Res. (in submission)
Drug Concentration of DCB
Nanoparticle incorporated
0.4
Magic Touch
1.2
Elutax
2
Moxy
2
Protege
3
AngioSculpt Scoring
3
Pantera Lux
3
Dior, Freeway
3
SeQuent Please
3
Cotavance
3
Wombat
3.3
IN. PACT
3.5
0
0.5
1
1.5
2
2.5
Drug dosage density on balloon (mcg/mm2)
3
3.5
4
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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