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Nanocardiology

January 2013
by

Shona Philip

on 13 November 2013

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Transcript of Nanocardiology

STENTS AND COMPLICATIONS
IDEAL STENT
RESEARCH
Nanocardiology
would limit its presence as a foreign object,
would minimize smooth muscle cell proliferation,
promote re-endothelialization
and eliminate thrombosis formation
1990s
Restenosis

Types of stents
Bare Metal Stent (BMS)
Drug Eluding Stent (DES)
Shona Philip
1st year medical student
Dalhousie University
Message
WHAT DOES A HEALTHY ARTERY LOOK LIKE?
Our
CURRENT
therapeutic interventions for cardiovascular disease such as percutaneous coronary intervention –
STENT THERAPY
are
NOT CURATIVE.
WHAT DOES A CARDIOLOGIST ENCOUNTER?
Goals of nanoparticles in stent therapy

reduce inflammation and thrombosis
reduce smooth muscle cell proliferation
promote re-endothelialization and modelling
WHAT TREATMENTS ARE AVAILABLE FOR ATHEROSCLEROSIS?
MESSAGE
The application of
NANOCARDIOLOGY
could benefit STENT THERAPY to
REDUCE
complications such as
RESTENOSIS
and to
PROMOTE

HEALTHY ARTERY
recovery
nanotechnology with coronary stent therapy
Coronary bypass sx
PCI - Stent therapy

BUT
this ideal stent does not exist currently
Nanocardiology has the potential to support ideal stent therapy

Payload - Paclitaxel
Targeting
- regiospecific permeability
Vivo
- balloon injured
Result
- 50% reduction in neointimal area in 4 wks
control
Pax NPs
Westedt et al, 2007
NP TARGETING
What are nanoparticles and why so special?
1–100 nm in size http://scaleofuniverse.com
Manipulation of NP fabrication
Improves regional drug pharmacokinetics/dynamics
Stents interact with the artery while nanoparticles gives us an opportunity to interact at a cellular level
How will nanoparticles work?
targeting (i.e. cell adhesion molecules, macrophages)
therapeutic payload (drugs, genes)
improved safety of localized effect


A healthy endothelium
vascular tone
cellular adhesion
thromboresistance
SMC proliferation
inflammation

lipid dysfunction
expression of chemotactic molecules
macrophage recruitment
remodelling
CONCLUSION
Restenosis
Stent therapy is not curative

Nanoparticles have a unique ability to target the cellular level

Nanoparticles can be used in various fields of cardiovascular medicine

A typical day in the cardiac future
Drawbacks of current research
non-specific targeting
adiministration variations
focus on SMC reduction, not re-endothelialization
BMS - restenosis: 16-44%
DES - restenosis -3-20%
Dysfunctional endothelium
length of lesion
geometry of artery
stent design and position

Payload - Rapamycin
Targeting
- alpha3beta3 integrin - specific targeting
Vivo
- balloon injured
Result
- 50% reduction in neointimal area in 4 wks
Cyrus et al, 2008

Payload -
Alendronate
Targeting
- macrophage specific targeting
Vivo
- balloon injured
Result
- 39.7% reduction in neointimal area in 30d
Cohen-Sela et al, 2006
First human trial
-
safety

Payload -
Paclitaxel
Targeting
- regio-specific permeability
Patients
- 23 pts - BMS
Result
- No adverse cardiac events. No restenosis in 30 and 70mg group at 6m
Payload
- Biphosphonate
Targeting
- macrophage specific targeting
Vivo
- balloon injured
Result
- reduction stenosis by 45% in 14 days but not 30days
RESEARCH
Margolis et al, 2007
CASE STUDY
Saint John Regional Hospital May 17, 2042

CC: Mr. Anderson - 97 y.o male with chest pain
Dx: acute MI, MVD

Treatment: 3XBRS (Lutchmedial-Brunt stent) in LAD, RCA, circumflex artery with thrombobegone IV NP therapy

48 hours later
Endo report - Dr. Chan
-only 20% re-endothelialization
-RX Endo-Grow NP single IV infusion

1 month later - f/u endoreport
-87% re-endothelization and 50% BRS resorbed

6 months later - BRS undetectable, 100 % re-endothelization, neointima growth <1%
Lobatto et al, 2011; Deanfield, 2007
Lobatto et al, 2011; Deanfield, 2007
Lobatto et al, 2011
Kibos et al, 2007
Kibos et al, 2007
Lobatto et al, 2011
Lobatto et al, 2011
Full transcript