-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.
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