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From Reparative Medicine to Nanomedicine

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Biomaterials, drug release and tissue engineering. Nanomedicine. 1) ... Important in patients with poor vascularity, diabetics (C) N. Ashammakhi, Nov 22, 2008 ... – PowerPoint PPT presentation

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Title: From Reparative Medicine to Nanomedicine


1
From Reparative Medicine to Nanomedicine
Prof N Ashammakhi, FRCSEd, PhD Keele
University
2
  • Innovation

Innovation
3
Check-list
  • Biomaterials, drug release and tissue engineering
  • Nanomedicine
  • 1) Particulate
  • 2) Fibres
  • 3) Patterns
  • 4) Combinations
  • Future

4
Dr Anna Barker, Deputy Director, National Cancer
Institute 2005
5

1. Biomaterials
6
Evolution
  • 1st Generation Bioinert materials
  • 2nd Generation Bioactive materials,
  • 3rd Generation Multifunctional materials

Ashammakhi Törmälä. J Craniofac Surg
7

Time
bone
Strength
Material
(C) N. Ashammakhi, Nov 22, 2008
8
  • 165 patients (161 children and 4 adults) were
    operated on (4 EU centers Paris, Innsbruck,
    London, and Oulu) from May 1, 1998 to January 31,
    2002.
  • Indications dyssynostotic deformities (n 159),
    bone defects after trauma (n 2), tumor removal
    (n 2), and treatment of encephalocele (n 2).
  • Plates 0.8, 1, or 1.2 mm thick. Screws (thread
    diameter 1.5 or 2 mm length of 4, 6, or 8
    mm). Tacks (outer diameter1.5 or 2 mm length
    of 4 or 6 mm).
  • Ashammakhi et al. J.
    Craniofac. Surg., 15 (4), 692-701, 2004

(C) N. Ashammakhi, Nov 22, 2008
9
Local DR
  • Produce high local levels of AB by diffusion
    which is not dependant on perfusion
  • Important in patients with poor vascularity,
    diabetics

(C) N. Ashammakhi, Nov 22, 2008
10

2. Nanomedicine
(C) N. Ashammakhi, Nov 22, 2008
11
Scale
  • Nanotechnology defines area of operation at
    1-100 nm (or even all submicron).
  • One nanometer a billionth of a meter the
    length of 10 hydrogen atoms placed end to end.

(C) N. Ashammakhi, Nov 22, 2008
12
Nano-medicine
  • In the US, National Nanotechnology Initiative
    lists medicine on the top of target beneficiaries
    form nanotechnology.
  • Nanomedicine established.
  • Procedures of repairing damaged cell organelles
  • n-particles, n-fibers, n-patterns, combinations.

(C) N. Ashammakhi, Nov 22, 2008
13
Nanomedicine
  • Nanotechnology for medicine.
  • Diagnosis, treatment (incl. prevention),
    monitoring and combinations.

(C) N. Ashammakhi, Nov 22, 2008
14
n-Forms
  • Particles
  • Fibres
  • Patterns/functionalisation
  • Combinations

(C) N. Ashammakhi, Nov 22, 2008
15

2.1Particulate
(C) N. Ashammakhi, Nov 22, 2008
16
np-Forms
  • n-particles, magnetic n-particles
  • n-capsules
  • Liposomes
  • Antibodies
  • Q-dots
  • Dendrimers
  • Others

(C) N. Ashammakhi, Nov 22, 2008
17
Targetting Strategies
  • Particle Size-based (pores in capillaries),
    uptake
  • Receptor
  • GFR, e.g. EGFR
  • Others folate
  • Antibody-based
  • Surface
  • Enzyme
  • Intracellular

(C) N. Ashammakhi, Nov 22, 2008
18
Targetting moietis
  • Monoclonal antibodies
  • Aptamers

(C) N. Ashammakhi, Nov 22, 2008
19
Targets
  • Ca cells
  • Ca vasculature

(C) N. Ashammakhi, Nov 22, 2008
20
Targeted therapies
  • More effective than current treatments
  • Less harmful to normal cells.

http//www.cancer.gov/cancertopics/factsheet/Thera
py/targeted
(C) N. Ashammakhi, Nov 22, 2008
21
Targeted therapies
  • Most are in preclinical testing
  • Some are in clinical trials or approved by FDA.
  • For use alone, in combination with each other,
    and in combination with other treatments, e.g.
    chemotherapy.

http//www.cancer.gov/cancertopics/factsheet/Thera
py/targeted
(C) N. Ashammakhi, Nov 22, 2008
22
siRNA
  • siRNA delivered in targeted manner employing
    transferretin, led to silencing of
    growth-promoting gene in Ewings sarcoma.

(C) N. Ashammakhi, Nov 22, 2008
23
Targets
  • A. To inhibit cell proliferation,
  • B. To induce apoptosis, or
  • C. Both.

http//ccjm.org/PDFFILES/Segota704.pdf
(C) N. Ashammakhi, Nov 22, 2008
24
NCI info
  • Information about these treatments can be found
    in the National Cancer Institute (NCI) fact
    sheets (on the Internet).

http//www.cancer.gov/ cancertopics/factsheet/Ther
apy/targeted
(C) N. Ashammakhi, Nov 22, 2008
25
Magnetic particles
  • n-particles with magnetic properties can be
    combined with fluorescent n-particles and applied
    for directing drugs to certain areas in a
    magnetic field.

(C) N. Ashammakhi, Nov 22, 2008
26
Triggered release
  • Triggered-release systems can be developed by
    using polymers responsive to changes in pH,
    temperature, magnetic fields, etc.

(C) N. Ashammakhi, Nov 22, 2008
27
Advantages
  • With current methods some of administered drug is
    lost, adding to cost.
  • Some of non-targeted drug may affect other organs
    giving rise to side effects.
  • Using targeted drug delivery, it will be possible
    to raise the dose and increase efficiency in
    future.

(C) N. Ashammakhi, Nov 22, 2008
28
Nerve
  • Magnetic nanoparticles (MNPs) and fields may be
    used to create mechanical tension that stimulates
    the growth and elongation of axons of the CNS
    neurons (DeSilva, MIAMI)

http//www.prnewswire.com/cgi-bin/stories.pl?ACCT
104STORY/www/story/05-20-2007/0004592038EDATE
(C) N. Ashammakhi, Nov 22, 2008
29
Particles for IVD
  • Introducing superabsorbent (hydrophilic
    polyelctrolyte) polymer granules, microspheres,
    n-particles, etc, into the intervertebral disc
    space without removing nucleus pulposus or
    annulus fibrosis material, to rehydrate the
    intervertebral disc space.

Trieu. US Pat Appl 20070150061 2005. DC
(C) N. Ashammakhi, Nov 22, 2008
30

2.2Fibres
(C) N. Ashammakhi, Nov 22, 2008
31
Glial scar
  • Self-Assembling n-fibers inhibit glial scar
    formation and promote axon elongation after
    spinal cord injury.  
  • Journal of Neuroscience, April 2, 2008,
    Vol. 28(14), pp. 3814-3823.

(C) N. Ashammakhi, Nov 22, 2008
32

2.3Patterns
(C) N. Ashammakhi, Nov 22, 2008
33
S. aureus
  • Poly(L-lysine)-grafted-poly(ethylene glycol)
  • (PLL-g-PEG) largely inhibits protein adsorption
    and the adherence of S. aureus to coated titanium
    surfaces.
  • Coating with (PLL-g-PEG/PEG-RGD) restores
    fibroblast and osteoblast attachment, whilst
    still inhibiting the adherence of S. aureus.

Harris et al. Biomaterials 2004, 25 (18) 4135
(C) N. Ashammakhi, Nov 22, 2008
34
Osteoblasts
  • More fibroblasts on smooth than on rough
    topographies,
  • Osteoblasts prefer rougher surfaces.

Schuler et al. Biomaterials 2006, 27 (21) 4003
(C) N. Ashammakhi, Nov 22, 2008
35
Combination
  • Combination of a surface n-patterning (block
    copolymer nanolithography) and a RGDfK peptide
    biofunctionalisation techniques.

Hirschfeld-Warneken et al. Eur J Cell Biol 2008
87(8-9)743
(C) N. Ashammakhi, Nov 22, 2008
36
Nerve
  • Nanotubes to guide axons
  • A combination of microlithography and chemical
    vapor deposition is used to engineer patterned
    vertical multiwalled carbon nanotube substrates.

Zhang et al. Sensors and Actuators B Chemical ,
2005, 106(2) 843-850
(C) N. Ashammakhi, Nov 22, 2008
37

3. Future
(C) N. Ashammakhi, Nov 22, 2008
38
Future
  • Personalized,
  • predictable and
  • controllable
  • therapy

(C) N. Ashammakhi, Nov 22, 2008
39
Thank you
(C) N. Ashammakhi, Nov 22, 2008
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