Biopolymer Processing in Medical Application as Vascular Stents
description
Transcript of Biopolymer Processing in Medical Application as Vascular Stents
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