nanotechnology in antidiabetic therapy.pptx

7/28/2019 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


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


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


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.

nanotechnology in antidiabetic therapy.pptx

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