Nano Microparticle Drug Delivery How will it play
- Slides: 11
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 Se. Quent Please B. Braun Melsungen AG Paccocath Paclitaxel 3 IN. PACT Medtronic-Invatec Free. Paclitaxel 3. 5 Dior, Freeway Eurocor Shellac Paclitaxel 3 Moxy Lutonix-Bard Nonpolymeric Paclitaxel 2 Pantera Lux Biotronik Butyryl-tri-hexyl citrate Paclitaxel 3 Angio. Sculpt Angio. Score unkonwn Protege Blue Medical unknown Elutax Aachen Resonance Wombat Magic Touch DCBPaclitaxel 6 x 60 mm; 1 inflation=3391 µg 3 Paclitaxel coated balloon= Paclitaxel 3 Low-dose (0. 2 μg/stent) No (2 layers of Paclitaxel 2 paclitaxel) Intermediate-dose (15 μg/stent) No (paclitaxel Avidal Vascular Paclitaxel 3. 3 wrapped) High-dose (187 μg/stent) Phospholipid based Heldman et al. Circulation. 2001; Concept Medical Sirolimus 1. 2 103: 2289 -2295 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 1 b (GP 1 b) § 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-Gp 1 b/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 Banerjee et al. J Cardiovasc Transl Res. (in submission)
Drug Concentration of DCB 0. 4 Nanoparticle incorporated 1. 2 Magic Touch Elutax 2 Moxy 2 Protege 3 Angio. Sculpt Scoring 3 Pantera Lux 3 Dior, Freeway 3 Se. Quent Please 3 Cotavance 3 3. 3 Wombat 3. 5 IN. PACT 0 0. 5 1 1. 5 2 2. 5 Drug dosage density on balloon (mcg/mm 2) 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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