Prof. David Woolfson

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Medical Device Issues
Prof. David Woolfson
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Medical Device A device implanted permanently or
temporarily in the body for a mechanical/structura
l purpose. Usually manufactured by extrusion or
injection-moulding (polymeric devices) Drug
Delivery Device A device intended to deliver a
drug for prophylactic or therapeutic purposes.
Usually, such devices control the rate at which
the drug is made available to the body
(controlled release devices Hybrid device A
medical device with a primary mechanical/structura
l function and a secondary drug delivery
function, either for device protection or
targeted drug delivery.
Devices
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Device- related problems

• Insertion pain tissue trauma
• Haemocompatibility
• Device encrustation - morbidity
• Device-related Infection - mortality
• gt250,000 device-related infections/year in the UK
  cost gt100million due to longer hospitalisation
  and more aggressive treatment
• There is now substantial interest in bioactive
  medical devices that encompass a drug delivery
  function

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Foley urinary catheter
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• Urinary catheterisation is frequently employed in
  clinical and domiciliary care of patients.
  Catheterisation may be short or long-term
  (indwelling, Foley-type) or intermittent
  (Nelaton-type)
• Catheter blockage due to encrustation with
  complex inorganic salts, resulting in device
  failure due to obstruction of flow, remains a
  major problem in longer-term use, as does
  device-related infection
• Tissue trauma due to insertion, and also upon
  removal, is a further problem with most types of
  catheterisation
• Surface formation of microbial biofilm, leading
  to UTI

Catheter issues
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ET TUBES from ICU PATIENTS at (clockwise) 4h, 8h,
12h
Endo- tracheal tube
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Biofilm formation
Surface of endotracheal tube retrieved from an
ICU patient
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Ureteral stents
from GORMAN SP et al BRITISH JOURNAL OF UROLOGY
73 (6) 687-691 1994
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Cardio- vascular stents
angioplasty balloon

mounted stent
stent in situ
Drug-Eluting Stents (stainless steel,
nitinol) The drug-eluting stent is basically a
bare metal stent that is then coated with a
slow-to-moderate-release drug formulation,
sometimes embedded in a polymer. It is hoped that
this will prevent or at least reduce restenosis,
reclosure of the coronary artery, one of the
biggest limitations of angioplasty and causes for
repeat procedures
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• The rapid evolution of clinical medicine exerts a
  continuing demand on manufacturers
• Manufacturers with a high cost base must add
  value to their lower-end products by making
  significant technological advances in order to
  compete with commodity suppliers, e.g. in
  continence care, respiratory, cardiovascular
  sectors
• Real clinical improvements are needed to
  demonstrate cost-savings to healthcare systems
  and justify higher reimbursement costs for
  healthcare systems
• Manufacturing and design improvements (e.g smooth
  device surface) not sufficient - bioactive
  devices ultimately required

Medical Devices - economics
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Medical Devices - polymers
poly(vinyl chloride) plasticised or unplasticised
poly(styrene) crystalline or amorphous (tacticity)
poly(ethylene) HDPE or LDPE
poly(urethane) HDPE or LDPE
silicone repeat unit crosslinked to form an
elastomer
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Device coatings

• Device coatings can add lubricity,
  biocompatibility, and antimicrobial action to
  device surfaces. Coatings can be used to release
  drugs or make implanted devices more visible to
  imaging systems
• Many device coatings are hydrophilic
  polymer-based formulations, usually hydrogels
• Enhanced device lubricity is one major reason for
  coating, e.g catheters and guidewires can be
  spray coated with a thin layer of
  polytetrafluoroethylene (PTFE)

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• Coatings may be applied to non-polymeric devices
  fabricated from stainless steel, platinum or
  nitinol (nickel titanium)
• Drug delivery coatings that render a device
  bioactive are now of major interest.
  Typically, a drug in a carrier hydrogel coating
  is released as the hydrogel imbibes water from
  surrounding biological fluids and swells
• Coating technologies presently include
  dip-coating, spray-coating, co-extrusion and
  chemical grafting to polymers, whereby the drug
  is added to the coating mix pre-process
• Relevant active agents include non-antibiotic
  antimicrobials, antibiotics and inorganic
  metallic elements such as silver

Bioactive coatings
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Controlled release mechanisms

• reservoirs (membranes)
• matrices (monoliths)

• diffusion controlled

• bioerosion/degradation
• pendant chain

• chemically controlled

• osmotic pressure
• swelling

• solvent activated

• externally smart controlled

• e.g. sensor-based

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Diffusion controlled systems
Matrix (monolithic)

• drug uniformly distributed through polymer
  matrix
• no danger of drug dumping
• first-order kinetics

• drug core surrounded by non-biodegradable polymer
• properties of drug and polymer govern diffusion
  rate
• drug-dumping if membrane ruptures
• zero-order kinetics from constant activity
  source

Reservoir
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Effect of bioactive agents released from silicone
Bioactive biomaterials
Miconazole nitrate
Nalidixic acid
Gentamicin sulphate
Ampicillin
Zone of Inhibition (mm)
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Time (days) of Repeated Microbial Challenge
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NewLEIF opportunities in bioactive biomaterials

• Alteration of surface topologies
  (nano-engineering)
• Direct implantation on devices surfaces
  (polymeric, metallic) of inorganic elements with
  antimicrobial properties, e.g silver , without
  the need for coating
• Surface implantation on preformed devices of
  organic compounds (MW lt 500) with antimicrobial
  activity through generation of highly charged
  species
• Laboratory and clinical assessments of efficacy