NANOTECHNOLOGY IN ANTIDIABETIC THERAPY.pptx
Transcript of NANOTECHNOLOGY IN ANTIDIABETIC THERAPY.pptx
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NANOTECHNOLOGYIN
ANTIDIABETIC THERAPY
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INTRODUCTION: NANOTECHNOLOGY AND DIABETES
MELLITUS
NANOMEDICINE APPLICATION IN GLUCOSE MONITERING
DRUGS USED IN THE TREATMENT OF DM
NANOCARRIERS FOR INSULIN DELIVERY
CONCLUSION
CONTENTS
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Nanotechnology is a field of applied science andtechnology which controls matter on molecular level in
scales within the 1-100 nm.
Nanometrology and nanotherapy
Deliver pharmaceuticals that cannot be effectively
delivered by conventional means.
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DIABETES MELLITUS
Metabolic disorder in which a person has high blood
sugar (200 mg/dl) - body does not produce enough
insulin or cells do not respond to the insulin.
Three types
Type I diabetes mellitus
Type II diabetes mellitus
Gestational diabetes
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Difference between Type I and Type II diabetes
mellitus
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150 million people
2025 : 300 million
Cardiovascular disease- hypertension
Renal failure
Retinal damage
Nerve damage
Microvascular damage
Poor healing
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The clinical need and the vision fornanotechnolgy in diabetes
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NANO MEDICINE APPLICATION IN GLUCOSE
MONITORING
1. Glucose nonosensors
2. Layer by layer (LBL) technique
3. Carbon nano tubes
4. Quantum dots
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1. GLUCOSE NANOSENSORS
Smart tattoo composed of glucose responsive,
fluorescence-based nanosensors implanted into the skin
but interrogated from outside the body, thus gives non-
invasive measurements.
The biological or artificial receptor for glucose - transduce
glucose concentrations into changes in fluorescence.
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Lectins : Plant lectin, Concanavalin
Enzymes : Hexokinase/ Glucokinase
Bacterial binding proteins :
Glucose Binding Protein (GBP)
Polarity sensing dyes : Nile red
Benzothiazolium squarine
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FRET - FLUORESCENCE RESONANCE ENERGY TRANFER
(Salinset al
., 2001)
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2. THE LAYER BY- LAYER (LBL) TECHNIQUE
Encapsulation of a glucose-sensing protein in nanoengineered microcapsules
The protein is adsorbed onto a template of calcium carbonate, alternatinglayers of poly-L-lysine and then poly-L-glutamic acid are applied, followed by
dissolution of the template using EDTA
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3. CARBON NANOTUBES
Single-walled carbon nanotubes (SWCNTs) fluoresce in theNIR spectral region.
Fluorophore probes
Dextran is bound to the carbon nanotubes
Binding of concanavalin A or apo-glucose oxidase to the
dextranSWCNT attenuates the fluorescence.
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Carbon nanotubes
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4. QUANTUM DOTS
Nanosized semiconductor crystals (210 nm)
Cadmium selenide coated with a shell - zinc sulfide.
Fluorescence - display high-intensity fluorescence that is
excitable over a broad range of wavelengths.
Emission wavelength dependent on the particle size.
Glucose displaces the concanavalin a labelled QDs from gold
labelled cyclodextrin, reducing the FRET and increasing the
fluorescence.
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DRUGS USED IN THE TREATMENT OF DIABETES
MELLITUS
1. Insulin Regular, Short, Long and ultra long acting
2. Oral hypoglycemic agents
Biguanides- Metformin
Sulfonylureas Glibenclamide, glipizide and
glyburide
Thiazolidinediones Rosiglitazone
Alpha-Glucosidase Inhibitors Acarbose
3. Islet cell transplantation
4.Pancreas transplantation
INSULIN THERAPY
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INSULIN THERAPY
Inconvenience of subcutaneous (SC) daily
High financial burden on health care cost
Insulin administered orally enters the portal circulation and
passes through the liver before reaching the systemic
circulation.
Oral Insulin - unstable in the gastrointestinal (GI) tract and low
permeability to cross the intestinal epithelium.
Hyperinsulinism
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Oral delivery of Insulin drug
(Ahmad et al., 2012))
THE CLINICAL NEED AND THE VISION FOR
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THE CLINICAL NEED AND THE VISION FOR
NANOTECHNOLGY IN DIABETES
Nanosize carriers have a large specific surface area
Protein encapsulation
Polymerization - Affects biocompatibility.
Polysaccharide - Chitosan
Mucoadhesion
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NANOCARRIES FOR INSULIN DELIVERY
1.Polymeric biodegradable nanoparticles
2. Polysaccharides and polymeric nanoparticles
3. Ceramic nanoparticles
4. Gold nanoparticle
5. Chitosan
6. Liposomes
7. Dendrimer
8. Polymeric micelle
9. Artificial pancreas
10. Antisense nucleotides (Subramani et al., 2012)
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POLYMERIC NANOPARTICLES
Solid, colloidal biodegradable polymers -10 to 100 nm.
Nanosphere and Nanocapsule
Nanosphere - matrix system in which the drug is physically
and uniformly dispersed
Nanocapsule - vesicular systems in which the drug is confined
to a cavity surrounded by a unique polymer membrane
These particles degrade into biologically acceptable
compounds by hydrolysis thus delivering the encapsulated
medication to the target tissue.
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Polyanhydrides
Polyacrylic acids
Polyurethanes
Poly (lactide - co - glycolide)
Polyesters and poly (methyl ethacrylates)
Methoxy poly(ethylene glycol)
N,N- dimethylaminoethyl methacrylate
Polyacrylamide
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Carriers of insulin
Polymer-insulin matrix surrounded by nano porous
membrane containing grafted glucose oxidase.
A rise in blood glucose level triggers a change in the
surrounding nano porous membrane causes alowering of the pH in the delivery system's
microenvironment.
Increase in the swelling of the polymer system,
resulting in biodegradation and subsequent insulin
delivery.
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(Dorski et al., 2011)
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POLYSACCHARIDES AND POLYMERIC NANOPARTICLES
Encapsulating the insulin molecules in polymeric
nanoparticles.
Calcium phosphatepoly(ethylene glycol) insulin
combination was combined with casein (milk protein).
Polysaccharides - Chitosan, dextran sulfate, and
cyclodextrin, - deliver the insulin molecules with
polymeric nanoparticles as carrier systems.
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Calcium phosphatePEGinsulincasein oral insulin delivery systemCAP - Calcium phosphate, PEG Poly ethylene glycol
BIOMEMS FOR INSULIN DELIVERY
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BIOMEMS FOR INSULIN DELIVERY
Biological micro electro mechanical systems
Drug reservoir compartment filled with insulin molecules
Biosensors and nano porous membranes with pores of 6 nm
diameter are located in the exterior to detect the changes in
blood glucose level and for insulin release.
Biocapsule consisting of two micromachined membranes
bonded together to form a cell-containing cavity bound bymembranes with nanopores.
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Biocapsule consisting of two micromachined membranes
bonded together to form a cell-containing cavity bounded by membranes
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Scanning electron micrographs of the microfabricated membrane of
6 nm pore size
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Monograph of biocapsule membrane with 24.5 nm pores
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Types of
nanoparticlesAdvantages Limitations
Polymeric
nanoparticles- Lesser cytotoxicity
- Higher target specificity
- High level of insulin
entrapment
- Ability to preserve insulin
structure and biological
activity
- Bypassing of the enzymatic
degradation in stomach
- Mucoadhesive
polymeric
nanoparticles
3 CERAMIC NANOPARTICLES
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3. CERAMIC NANOPARTICLES
Calcium phosphate, silica, alumina or titanium.
Easier preparative processes, high biocompatibility ultra-
low size (less than 50 nm) and good dimensional stability
Protect the doped drug molecules against denaturationcaused by changes in external pH and temperature.
Do not undergo swelling or porosity changes caused by
changes in surrounding environment.
Types of Advantages Limitations
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Types of
nanoparticlesAdvantages Limitations
Ceramic nanoparticles - Easy preparativeprocesses
- High biocompatibility
ultra-low size (less
than 50 nm)
- Good dimensional
stability- Protection
- Manufactured with
desired size
shape
porosity
- Poor permeability
across the
mucosal membrane
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4.GOLD NANOPARTICLE
Chitosan - reducing agent in the synthesis of gold
nanoparticles and promoted the penetration and uptake
of insulin across the oral and nasal mucosa
Long term stability
Improved pharmacodynamic activity of insulin.
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Types of
nanoparticlesAdvantages Limitations
Gold nanoparticles - Long term stabilityin terms of
aggregation and
good insulin
loading
- Higher uptake of
insulin across oral
& nasal mucosa
- Improved
pharmacodynamic
activity of insulin
Widespread distribution
in organs like liver, lung,
spleen,
kidney, brain, heart,
stomach
and joints
5 CHITOSAN
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5. CHITOSAN
Cationic polysaccharide synthesized by partial deacetylation of
chitin (polymer found in crustacean shells and insects)
Glucosamine and N-acetyl-glucosamine
Carrier system - Protect insulin in the stomach and small
intestine
Enhanced the intestinal absorption of insulin
Mucoadhesive - prolong their residence in the small intestine,
infiltrate into the mucus layer and subsequently mediate
transiently opening the tight junctions between epithelial cells.
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MICROSPHERE
Protease inhibitors by protecting the encapsulated
insulin from enzymatic degradation within its matrix
Permeation enhancers - effectively crossing the
epithelial layer after oral administration
LIPOSOMES
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LIPOSOMES
Spherical, self-closed structures formed by one or
several concentric lipid bilayers with an aqueous phase
inside and between the lipid bilayers.
Vehicle for delivery of insulin
Lecithin 100mg, cholesterol 20mg, insulin 150units,
Tween 1%.
The effect of insulin lioposome was prolonged in diabeticinduced rats than the normal rats.
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T f Ad t Li it ti
http://en.wikipedia.org/wiki/File:Liposome_scheme-en.svg -
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Types of
nanoparticlesAdvantages Limitations
Liposomes - Biodegradable- Non-toxic
- Non-immunogenic- Captured by the
human bodys defense
system (RES)
- Post-treatment
accumulation in skin
and eyes
DENDRIMER
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DENDRIMER
1978 - Fritz
Hydrophobic, branched molecules, spherical polymers with
coreshell nanoarchitecture.
1 to 10 nm.
Dendrimer encapulated nanoparticles.
Encapsulation of hydrophobic compounds and for the
delivery of drugs.
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POLYMERIC MICELLE
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POLYMERIC MICELLE
Lipid-core micelles - conjugates of soluble copolymers
with lipids (polyethylene glycophosphatidyl ethanolamine
conjugate).
Colloidal particles with a hydrophobic core and
hydrophilic shell are currently successfully used as
pharmaceutical carriers for water-insoluble drugs.
Spherical in shape.
High stability both in vitro and in vivo
Good biocompatibility
Enhanced permeability and retention
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ARTIFICIAL PANCREAS
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ARTIFICIAL PANCREAS
Tiny silicon box - pancreatic beta cells taken from animals.
Box is surrounded by a material with a very specificnanopore size (20 nm in diameter)
Boxes can be implanted under the skin of diabetes
patients
A sensor electrode repeatedly measures the level of blood
glucose; this information feeds into a small computer that
energizes an infusion pump and the needed units of insulin
enter the bloodstream from a small reservoir.
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ANTISENSE OLIGONUCLEOTIDES
Short strands of deoxyribonucleotides that are
complementary to specific encoding mRNA sequences
and can block gene expression
Helps drugs to avoid the bodys defences that the drug
encounters following its systemic administration.
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CONCLUSION
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CONCLUSION
Diabetes is a rapidly growing global problem, which requires
management at the patient level, via blood glucose control to
prevent worsening effects of the disease.
Applications of nanomedicine in diabetes are in their infancy
and none have reached routine clinical use.
To date, there have been no approved oral insulin
nanoformulations. This is probably due to the difficult
requirements that need to be met by the drug preparations.
In order to be successful, orally administered insulin nano-
carriers must have efficient delivery system to increase insulin
bioavailability to reach therapeutic levels
These drug delivery technologies are in various stages of
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These drug delivery technologies are in various stages of
research and development. It is expected that these
limitations can be overcome and the discoveries to come into
practical use within the next 5-10 years.
Scientific community hasnt yet understood completely how
the human body would react to these nanoparticles and
nanosystems, which are acting as drug carriers.
Nanomedicine is at a very early stage, but progress is rapid,
translational, expansive and multi-purpose.
In future nanomedicine is likely to be a key technology for
solving diabetes problem.