-Dr .Anupam Das

PG MD Pharmacology

GSL medical college

Nanomedicine is the process of diagnosing,

treating, and preventing disease and traumatic

injury, of relieving pain, and of preserving and

improving human health, using molecular tools and

molecular knowledge of the human body.

Nanotechnology in medicine involves applications

of nanoparticles currently under development, as

well as longer range research that involves the use

of manufactured nano-robots to make repairs at

the cellular level .

Definition

Nanopharmacology can be defined as

the application of nanotechnology to the

development and/or discovery of methods to

deliver drugs.

The word nano is a scientific prefix that stands for one-billionth; the word itself comes from the Greek word “nanos”, meaning dwarf.

Nanoparticles have one dimension that measures 1000 nanometers or less.

Colloidal systems.

The properties of many conventional materials change when formed from nanoparticles. This is typically because nanoparticles have a greater surface area per weight than larger particles which causes them to be more reactive to some other molecules.

Buckyballs, also called “fullerenes”, were one

of the first nanoparticles discovered in 1985 at

Rice University.

Buckyballs are composed of carbon atoms

linked to three other carbon atoms by covalent

bonds.The carbon atoms are connected in the

same pattern of hexagons and pentagons

Buckyballs are used in composites to

strengthen material.

NANOPORES

QUANTUM DOTS and NANOCRYSTALS

FULLERENES and NANOTUBES

NANOSHELLS and MAGNETIC

NANOPROBES

TARGETED NANOPARTICLES and SMART

DRUGS

DENDRIMERS and DENDRIMER based

devices

RADIOCONTROLLED BIOMOLECULES

Simplest medical nanomaterials.

Created by Desai and Ferrari in 1997.

Large enough for glucose, insulin and oxygen

to pass but small for immune system

molecules.

Valuable for enzyme or hormone deficiency

diseases.

Could also be considered for diseases like

Alzhimer’s and Parkinsons.

Nanosieve – fabricated by Martin in 1995.

Regulation of flow of materials through

nanopores.

1998-2000 Daniel Branton conducted

experiments to drive RNA and DNA polymers

through nanopores by using an electric field.

PRESENT SCENARIO : fabrication of pores

allowing a single strand of DNA to pass through

the pores.

Injected nanomaterials from blood

collect in tumor tissue and can be

used as imaging agents

Tumor

Tumor

cells

Drug-carrying

nanoparticle

Nanomaterials Used as Drug Carriers or Contrast Agents for In Vivo

Cancer Applications.

Tiny particles measuring only a few

nanometers.

Colors can be customized by varying particle

size or composition.

Useful for studying genes, proteins , tissue

specimens.

They are also being investigated for cancer cell

detection, DNA microarray analysis , drug

screening , vascular imaging ,

immunocytochemical probes.

Already undergoing clinical trials.

Good biocompatibility and low toxicity.

Antiviral agents(mainly HIV)

Antibacterial agents(against E.Coli

,mycobacterium, streptococcus)

Anti apoptosis (for ALS)

The properties of buckyballs (also known as fullerenes) have caused researchers and companies to consider using them in several fields

Buckyballs may be used to trap free radicals generated during an allergic reaction and block the inflammation that results from an allergic reaction.

The antioxidant properties of buckyballs may be able to fight the deterioration of motor function due to multiple sclerosis.

Nanotubes bound to an antibody that is

produced by chickens have been shown to be

useful in lab tests to destroy breast cancer

tumors.

Improving the healing process for broken

bones by providing a carbon nanotube scaffold

that new bone material can grow around.

Using nanotubes as a cellular scale needle to

deliver quantum dots and proteins into cancer

cells.

Biosensors to detect glucose, ethanol,

immunoglobulins.

Halas and West at Rice university developed a drug delivery system called “nano-shell”.

Larger in size than fullerenes.

Considered for cancer treatment.

May also be considered for treatment of diabetic patients.

Triton Biosystems – binding of iron nanoparticles to monoclonal antibodies and put into nanobioprobesabout 40 nm in size.

Bind to tumor cell membranes,magnetic field created by porable machine and heat is generated, damaging the tumor cells.

Gold and nickel nanorods as tissue carriers for

gene delivery.

Attachment of Dna plasmids to nickel and

transferrin to gold.

“CANCER SMART BOMBS”

Under investigation :alpha emitting actinium

based “nanogenerator”.

Enzyme activated drugs.

NANOSOMES- dynamic nano platform.

Use of polymers for drug delivery.

Ideal polymer.

Currently used biodegradeable polymers are:

POLY 2HYDROXYETHYL METHA-ACRYLATE

POLY N-VINYLPYROROLIDONE

POLY ETHYLENE GLYCOL

Some polymers that degrade within the body are:

PLA- polylactides.

PGA- polyglycolides.

PLGA – polylactide co glycosides.

Polyanhydrides.

Nanostructural material.

STARBURST dendrimers

GLYCODENDRIMER : “NANODECOYS”.

TECTODENDRIMERS.

Single core , surrounded by additional

dendrimer modules of different types.

Diseased cell recognition

Diagnosis of diseased state.

Drug delivery

Reporting location

Reporting outcome of therapy.

Mid 2002, James Baker’s lab at University of

Michigan came up with a dendrimer that could

detect caspase3 , an enzyme released during

apoptosis.

Research was funded by NASA and National

Cancer Institute.

Used to detect radiation induced cellular

damage in astronauts.

Attachment of tiny radiofrequency antennas to

DNA.

Magnetic field induces highly localized heating

process that separates the double stranded

DNA into two single strands.

Maybe of help in gene regulation.

NANOSPHERES

NANOCAPSULES

SOLID LIPID NANOPARTICLES(SLN)

POLYMERIC nanoparticles

CERAMIC nanoparticles

HYDROGEL nanoparticles

COPOLYMERIZED nanoparticles

NANOSUSPENSIONS

NANOWIRES

FUNCTIONALIZED NANOCARRIERS

LIPOSOMES

1. DRUG DELIVERY TECHNIQUES.

2. THERAPEUTIC TECHNIQUES.

3. DIAGNOSTIC APPLICATIONS.

4. CELL REPAIR.

SOLVENT PRECIPITATION TECHNIQUE

SOLVENT EVAPORATION TECHNIQUE

SPRAY DRYING

PHASE SEPARATION

DESOLVATION OF POLYMER BY CHEMICAL

rxn.

DESOLVATION OF POLYMER BY SALT

ADDITION.

High speed centrifugation.

Ultrafiltration.

Freeze drying.

CHEMICAL STABILITY

-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY.

PHYSICAL STABILITY

-particle size

-design of freeflowing nonoparticulate powder-lubricants, glidants

-design of stable nanosuspensions – low sedimentation, good redispersibility, minimum drug leaching during shelf life

Bioadhesion test has to be done.

Evaluation as per ICH guidelines

- In ambient condition

- At temp of 40 degree celcius+/-2 with RH 75+/-

5%

- At temp of 30 degree celcius +/-2 with RH

60+/-5%

Size

Higher drug loading

Solubility

Large surface area

Intracellular uptake-nanometer size range

particles more efficiently taken up than

microparticles

Charge - Surface charge influences plasma

protein binding and cellular uptake

Enhanced drug stability

High carrying capacity

Hydrophilic/hydrophobic substances

Enhance absorption and bioavailability

Reduce clearance

Minimal first pass metabolism

Increase in drug half life leading to prolonged effect

Through slow release can reduce dosage and dose frequency

Selective uptake by tissues (passive targeting)

Delivery through lymphatic system

Target specific tissue and cells (active targeting)

Increase bioavailability.

1.NANODISPERSIONS

-Nanosuspensions

-Nanoemulsions

-Niosomes

2.POLYMERIC and NOMPOLYMERIC

NANOPARICLES

3.POLYMERIC MICELLES

•Improve the PK of anti-TB drugs

Sustained release

Improve solubility and half-life

•Reduce dose frequency

Polymer degradation: Sustained release over days

•Reduce dose

Deliver drug at site of action

•Reduce treatment time and cost

6-9 months: potentially 2 months

Current drugs cost: 1% of the total treatment management

Successfully nano encapsulated 4 of the

first line anti-TB drugs

•Isoniazid (INH), Rifampicin (RIF), Pyrazinamide

(PZA) and Ethambutol (ETB)

•Poly (lactide-co-glycolide) (PLGA) polymer

•Nanoencapsulated anti-TB drugs as effective

as conventional drugs at fraction of dose

Implications of nanomedicine to improve TB

drugs.

Reduction in the dose frequency.

Promoting patient compliance to treatment.

Targeting next step to reduce dose.

Can be applied to malaria, HIV and other

poverty related diseases

Theoretical engineering design.

Artificial red blood cell.

Internal pressure of 1000 atmosphere.

Can hold 236 times more O2 and CO2 than an

RBC.

Three design components : O2 , CO2 and

Glucose.

Diamond chambers.

Emergency conditions as blood substitute.

Anemia

SIDS

Asthma and other respiratory diseases.

Maintain tissue oxygenation.

Super human ability in sports.

Futuristic micromachine containing numerous

nanomachine systems.

Invented by Robert .A. Freitas.

Geometric volume of 12.1 microns.

Components: binding port, ingestion port,

digestion port and exhaust.

80 times more efficient and 1000 times faster

than natural WBC.

act as a semi-autonomous on-site surgeon

inside the human body.

maintaining contact with the supervising

surgeon via coded ultra sound signals

FEMTOLASER- “nano scissors”.

Femtolaser surgery has performed the following:

Localized nanosurgical ablation of focal adhesions adjoining live mammalian epithelial cells.

Microtubule dissection inside yeast cells.

Noninvasive intratissue nanodissection of plant cell walls and selective destruction of intracellular single plastids.

Nanosurgery of individual chromosomes (selectively knocking out genomic nanometer-sized regions within the nucleus of living Chinese hamster ovary cells.

Elimination of isolated cancer cells.

Removal of microvascular obstructions.

“noninvasive” tissue transplant.

Exchange of new chromosomes for old ones.

Molecular repairs.

DISADVANTAGES OF NANOMEDICINE:

Cost of treatment will be high.

Manufacturing defects.

Low clinical trials.

Physician reaction to newer modalities.

Machine to machine interactions.

Potential to change the face of the Medical

field.

Boon for patients suffering from untreatable

conditions.

Removes need of daily tablets, injections, long

surgical and diagnostic procedures.

However affordability remains an issue.

Inadequate number of clinical trials.

Medicine update vol 23, ch85,86, 2013.

Postgraduate topics in pharmacology 1st

ed,168-169,187-188.

Robert .A. Freitas,Jr. ,Journal of Computational

and Theoretical NanoscienceVol.2, 1–25, 2005

www.int-journal-surgery.com

http://thenanoage.com

http://www.foresight.org/Nanomedicine

Betty Y.S.Kim et al NEJM ,2434-2443,dec

2010.