Applying Nanotechnology toApplying Nanotechnology  to Coronary heart disease

S. Sundar Manoharan, Department of ChemistryIndian Inst of Technology Kanpur

Manifestations : Angina, Heart attackCrisis : Ischemic heart diseaseManifestations : Angina, Heart attack

and Heart failureExisting remedy: Angioplasty

STENT ANGIOPLASTY

900,000 stent procedures done per year in USA alone against 20,000 in India

Drug Paclitaxel

Multi- functionalInterrupts Restenotic cascade

Schematic representation of biodegradable (bioerodible)drug delivery device

There are three major components to a drug‐

eluting stent: 

Type of stent that carries the drugType of stent that carries the drugcoating

Method by which the drug isy gdelivered (eluted) by the coating tothe arterial wall (polymeric or other)the arterial wall (polymeric or other)

The drug itself – how does it act inthe body to prevent restenosis?the body to prevent restenosis?

THROMBOSIS

TWO FOLD Challenges : In-stent Restenosis and Thrombosis

Problem addressed by the Industry:

Use Drug Eluting Stents(800 USD) instead of Bare Metal Stents(2200 USD),

S SHowever DES leads to thrombosis and BMS leads to Restenosis.

(A) (B)

(C) (D)

Image courtesy:  JACC 50, S 55(2010)

Technology Description

Technology is to employ a Nano polymercoating which would avoid the postg pstenting crisis such as catastrophiccomplication of acute thrombosis, and In-stent restenosis

By means of ……..y fState of the art deposition technique for nanocoatingInexpensive, biocompatible and chemically inert materialTotally feasible for large scale production & clinical trialsTotally feasible for large scale production & clinical trials

The Developed Technology(c)

(b) (a.u

.)

Novelty of this coating

•Stent inert

(a)

( )

204)

00)

0)I N T

E N

S I T

Y

(100

)

• Reduce platelet adhesion

• Prevent acute thrombosis(clotting ).

10 20 30 40 50

(2(20

(110

2Novelty of this innovation:

90

100

nce

(%)

PED D eposited film

B ulk

innovation:

The material coated is new

70

80

512

644

1156

Tran

smitt

an

1220

The process to coat in nm is new

The time scale needed for deposition < 2 hours

1500 1000 500W avenum ber (cm -1 )

deposition 2 hours

Low cost production

SEM IMAGE OF UNCOATED SURFACE

SEM IMAGE OF COATED SURFACE

Coated Co Milling

Biocompatibility

Nano coated vs bare stentNano coated vs bare stent

In vitro exposure to human bloodblood

Coated stent surface

Nanocoated and baremetal stent exposed to platelets

Uncoated stent surface

Excellent biocompatibility established for Nano coated stents

Stent Market Analysis

Global Stent device market is $ 6 Billion  40

50

60

market is $ 6 Billion (USA 43%)

Competition is for bare  10

20

30

Stent market inCompetition is for bare 

metal stents($ 800) and drug coated stents ($ )

0

Global % USA %

market in $

($2300). FDA (USA) or CE 

(Europe) approval  1500

2000

2500

(Europe) approval dictates the clinical trials 500

1000

1500

cost of stents in $

0

bare stents drug coated

900,000 stent proceedures done per year in USA alone

J & JMedtronicsAbbottBoston

CeloNova BioSciences,Atlanta

Important pointers from this Innovation: Prospects for a Third generation Stent involving Nanotechnology

Solution and differentiators

BiocompatibilityNovelty of this invention Value Proposition

Nano coated vs bare stentwere In vitro exposed to human blood

y

•Stent inert

• Reduce platelet adhesion

• Global Stent device market is $ 4.2 Billion (USA 43%)/per year

fExcellent biocompatibility and anti platelet adhesion 

• Prevent acute thrombosis clotting

•The material coated is new

• Competition is for bare metal stents($ 800) and drug coated stents ($2300)

• Our innovation will properties  were seen on Nano‐coated stent surface.

•The process to coat in nm is new

•The time scale needed for deposition< 2 hours

• Our innovation will provide stents at 800 USD with anti restentosis and anti thrombosis effect .

Large platelet adhesion seen on Bare metal stents‐showing high risk f th b i

•Low cost production • This is the first of its kind from India where a Nano‐ coated stent is developed

for thrombosis.

ths

FDA

mon

t

& CE

Time line for future activities

Current Status

Currently the company is incubated at the SIDBI center at IIT Kanpur (since Feb 2010)( )

Capital seed fund from MSME‐IITK .

TePP Phase II grant DSIR (committed), Liasoning through FICCI)

TDB grant committed  by DST( This innovation won the Gold medal for the DST‐LOCKHEED MARTIN  INDIA GROWTH INNOVATION PROGRAM 2009  and was specifically identified for funding  by the DST).

NDA  signed with American Cardiovascular Imaging company to initiate s g ed t e ca Ca d o ascu a ag g co pa y to t ateclinical trials at USA laboratories and to raise VC funding for animal studies

NDA signed with Opto Circuits for providing Stent platform and for NDA signed with Opto Circuits for providing Stent platform and for Animal studies to be carried out at Vienna‐Austria

INDIAN PATENT AND PCT FILED i  J      d  J     INDIAN PATENT AND PCT FILED in June  2009 and  June 2010 respectively

Risks

IPR issues  

Risks

IPR issues. 

International competition (cf: Catania stents reported  by Dr CorradoTamburino (Ferrarotto Hospital, Catania, y ( p , ,Italy, April 2009). 

The next 12‐18 months is crucial in taking the product l l t  Cli i l   t   level to Clinical  stage.  

Out of Intense complexities Intense simplicities emerge

…. Winston Churchill

After 90 days With Drug ‐ Paclitaxel After 90 days Without Drug

MOTIVATION: Coronary stent has emerged over theMOTIVATION: Coronary stent has emerged over theyears to be the established platform strategy forinterventional procedures performed in all modern dayp p ycardiac catheterization laboratories. Unfortunatelymany of these patients(20 to 40%) develop anexaggerated vascular neointimal proliferation afterstenting namely, in stent restenosis. On the other hand,Drug Eluting Stents bring in late stent thrombosisDrug Eluting Stents bring in late stent thrombosis.New generation stents are needed to abolish restenosisand thrombosis without compromising safety.and thrombosis without compromising safety.

Coated stent surface

Nanocoated and baremetal stent exposed to plateletsplatelets

Uncoated stent surface