BIOPOLYMER PROCESSING IN MEDICAL APPLICATION AS

VASCULAR STENTS

Reviewed by:AGNES Purwidyantri

Student ID No: D0228005

Biodegradable Polymers as Drug Carrier Systems

Polyesters Lactide/Glycolide Copolymers

Have been used for the delivery of steriods, anticancer agent, antibiotics, etc.

PLLA is found as an excellent biomaterials and safe for in vivo (Lactic acid contains an asymmetric α-carbon atom with three different isomers as D-, L- and DL-lactic acid)

PLGA is most widely investigated biodegradable polymers for drug delivery.

Lactide/glycolide copolymers have been subjected to extensive animal and human trials without any significant harmful side effects

Biodegradable Polymers as Drug Carrier Systems

Poly(amides) Natural Polymers

Remain attractive because they are natural products of living organism, readily available, relatively inexpensive, etc.

Mostly focused on the use of proteins such as gelatin, collagen, and albumin

Biodegradable Polymers as Drug Carrier Systems

Polymer Processing Drug-incorporated matrices can be formulated

either compression or injection molding Polymer & drug can be ground in a Micro Mill,

sieve into particle size of 90-120 µm, then press into circular disc

Alternatively drug can be mixed into molten polymer to form small chips, then it is fed into injection molder to mold into desired shape

What is a Stent? A small tubular mesh usually made of

either stainless steel or Nitinol. Inserted into stenotic arteries to keep the

lumen patent often used after PTCA. Used at various sites including the

coronary, renal, carotid and femoral arteries.

Non-arterial uses e.g. in bronchus, trachea, ureter, bile duct.

Current stent designs

Palmaz, the market leader

Palmaz “Corinthian” Iliac artery stent

Gianturco-Roubin II Stent

History The concept of vascular stents is

accredited to Charles Dotter in 1969, who implanted stainless steel coils in canine peripheral arteries. Not followed up in humans because of

haemodynamically significant narrowing. Not in clinical practice until 1980s. Market leader is the Palmaz stent

designed by Julio Palmaz in 1985. Initially, 18 grafts placed in canine vessels,

with patency rates approaching 80% at 35 weeks.

Plaque Formation and Morphology

Smoking, high BP, toxins etc cause damage to the vascular endothelium.

LDL and fibrin pass through and collect in the sub-endothelium.

Monocytes adhere to the damaged endothelium, migrate to the sub-endothelial space and engulf LDL – FOAM CELLS.

SMC migration and CT formation. Two main types of plaque:

Atheromatous (athere: gruel, oma: tumour) Fibrous (like atheroma but with connective tissue cap)

CVD statistics Heart and circulatory disease is the UK's

biggest killer.  In 2001, cardiovascular disease caused

40% of deaths in the UK, and killed over 245,000 people.

Coronary heart disease causes over 120,000 deaths a year in the UK: approximately one in four deaths in men and one in six deaths in women.

Revascularisation techniques

Coronary Artery Bypass Graft (CABG) Percutaneous Transluminal Coronary

Angioplasty (PTCA) Stents

CABG Major surgery Complications

Stroke Mediastinitis (1-4%) Renal dysfunction (8%)

Minimally invasive procedure Percutaneous access

either in the brachial or femoral arteries.

A guide wire is advanced to the stenotic region.

A balloon is advanced along the wire and inflated/deflated several times to fracture the plaque and open the lumen.

PTCA

Complications of PTCA Plaque rupture, may lead to:

Thrombus formation Intimal flap

Arterial rupture Acute closure Sub-optimal result Restenosis

Requires further intervention to make vessel patent

Stenting vs. PTCA Prevents acute closure Tacks back intimal flaps Less restenosis:

30–50 % restenosis with PTCA (coronary arteries).

Coronary stents are associated with fewer repeat revascularisation procedures

Rates of death and MI are low and are not significantly different between stents and PTA.

Stent Failure- Stenosis (20-30%

i shear stress Intimal Hyperplasia i lumen h shear stress If baseline shear stress not restored –

continuing intimal hyperplasia and RESTENOSIS

Factors Which Contribute to In-stent Restenosis

Thrombus/platelet/fibrin adherence to stent struts. Metabolic disorder/smoking/atherogenic diet. Small lumen diameter. Stress concentration at end of stent. Flow disturbance within stented region.

Thrombus in Human Coronary Artery

Improving Vascular Stents (1)

Thrombus Anticoagulants

Heparin – systemically or coated on stent. Inhibition of the GP IIb-IIIa receptor:

Prevents platelet aggregation. Available as Abciximab. Associated with h incidence of MI.

PTFE coated stents.

Intimal hyperplasia in stented Canine iliac artery.

After insertion of stent plus PTFE graft material.

Improving Vascular Stents (2)

Small diameter artery Combination of local and systemic medication

and covered stents. Intimal hyperplasia

Brachytherapy: Use of ionising radiation to stop cellular proliferation. Delivery: Radioactive stents, catheter radiation. 10% restenosis but may cause necrosis.

Anti-proliferative agents e.g. rapamycin (Sirolimus)

Improving Vascular Stents (3)

Mechanical and flow disturbances: Compliance Matching Stent (CMS)

This stent is rigid in the middle and becomes more compliant near its ends.

This compliance is achieved by parabolic and cantilevered struts.

The middle struts are straighter, providing some resistance to recoil and support for the atherosclerotic plaque.

Compliance Matching Stent

Parabolic and canti-levered struts causeends to be mostcompliant.

Straighter struts inmiddle provide stiffsupport for plaque.

Transition in between.

Compliance Matching Stent

The gradual change from rigid to compliant with the CMS reduces stress concentration at the stent edges.

The geometry of this stent also fosters more laminar flow through the stent.

Less flow disturbance means less intimal hyperplasia.

Bioabsorbable Stents Durable polymer coatings on drug-eluting

stents have been associated with chronic inflammation and impaired healing.

• Reduced Polymer Load• Short-term Polymer

Exposure

• Reduce DAPT duration• Reduce risk with DAPT

interruption• Decrease stent thrombosis

may

Potential advantages of bioabsorbable polymer stents:

SYNERGY Stent Bioabsorbable polymer (PLGA) Applied only to the abluminal surface (rollcoat)Thin strut (0.0029”) PtCr Stent

Durable PermanentPolymer

+Drug

360° AroundStent

PLGA BioabsorbablePolymer

+Everolimus

on Abluminal Side of Stent

Abluminal Bioabsorbable Polymer

Current Durable Polymer

Abluminal Bioabsorbable Polymer