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Nanopharmacology
1. Nanopharmacology
Mohanad AlBayati
Mohanad AbdulSattar Ali Al-Bayati, BVM&S, MS, PhD
Assistant Professor of Pharmacology and Toxicology
Department of Physiology and Pharmacology
College of Veterinary Medicine
University of Baghdad
Al Ameria, Baghdad
Phone: 0964 7802120391
E. Mail: aumnmumu@covm.uobaghdad.edu.iq
aumnmumu@yahoo.com
2. Nanotechnology
Nanotechnology is a complex of scientific knowledge,
methods and means aimed at controllable assembly
(synthesis) of various substances, materials and items
with the linear size of structural elements of up to 100
nm (1 nm – 10-9 m; 1 nm = 10 Ǻ ) from individual
atoms and molecules.
6. PROSPECTS OF INVESTIGATIONS
1. Development of new technologies of nanoparticles
manufacturing, especially composites of organic and
inorganic origin.
2. Design of new dosage forms for external and
internal application and inhalation.
3. Study the therapeutic mechanisms of action of
new nanodrugs.
4. Investigations of nanomaterials toxicity.
8. Nanopharmacology
History
The term Nanotechnology was first introduced on December
29, 1959, in a talk at the annual meeting of the American Physical
Society at the California Institute of Technology by the Nobel Prize-
winning physicist Richard Feynman (Nobel Prize for Physics 1965),
entitled “There’s Plenty of Room at the Bottom”. He proposed to use a
set of conventional-sized robot arms to construct a replica of
themselves, but one-tenth the original size, then using that new set of
arms to manufacture an even smaller set, and so on, until the
molecular scale is reached. This discussion was the earliest vision of
nanotechnology
9. Nanopharmacology is the use of nanotechnology for discovery of new
pharmacological molecular entities; selection of pharmaceuticals for specific
individuals to maximize effectiveness and minimize side effects; and delivery
of pharmaceuticals to targeted locations or tissues within the body.
Drug Effectiveness :
1. MOA
2. Delivery
3. Right concentration
4. coverage
5. Elimination
Liposome's Polymeric Nanoparticles
10. Type of Nanoparticles Material Used Application
1 Polymeric Nanoparticles Biodegradable Polymers
Controlled and targeted
drug delivery
2 Quantum Dots CdSe–CdS core-shell
Targeting, Imaging
Agent
3 Nanopores
Aerogel, which is produced by sol-
gel chemistry
Controlled release drug
carriers
4
Nanowires or
CarbonNanotubes
Metals, semiconductors or carbon Gene and DNA delivery
5 Nanoshells coated with gold
Dielectric (typically gold sulfide or
silica) core and a metal (gold)
shell.
Tumor Targeting
6 Liposomes Phospholipid Vesicles
Controlled and targeted
drug delivery
7 Ceramic nanoparticles Silica, alumina, titania
Drug targeting, Bio-
molecules delivery
8 Polymeric micelles Amphiphilic block copolymers
Systemic and controlled
delivery of water-
insoluble drugs
9 Polymeric Nanoparticles Biodegradable Polymers
Controlled and targeted
drug Delivery
11. TABS
Nano fact
Nanomaterials are all nanoscale materials or materials that
contain nanoscale structures internally or on their
surfaces. These can include engineered nano-objects, such
as nanoparticles, nanotubes, and nanoplates, and
naturally occurring nanoparticles, such as volcanic ash,
sea spray, and smoke
12. TABS
Nanoscale
Fundamental Nanoscale Phenomena and Processes, General, NNI
Budget and Strategy, Nanomaterials, Nanoscale devices and Systems,
Instrumentation Research, Metrology and Standards for
Nanotechnology, Nanomanufacturing, Major Research Facilities and
Instrumentation Acquisition, Environmental Health and Safety,
Educational and Societal Dimensions, Solar, Electronics
13. Nanotechnology in pharmacology
• Drug acquisition
• Drug storage and dispensing
• Safety and caregiver exposure during drug administration
• Need for new protective equipment
• Inability to retrieve defective drug or chip or robot once administered
• Defective nanodrug or application
• Access
• Effects over a lifetime and toxicity
• Decay over time
• Predictability
• Unknown interactions
• Human-environment-animal transmission
15. Nanopharmacology of liposomes
Nanopharmacology of liposomes involves the use of nanoliposomes with
novel pharmacological principles, such as favorable pharmacokinetics, to
maximize efficacy and minimize the adverse effects of drugs, including
drug delivery to targeted locations or tissues (e.g., cancer cells).
Liposomes are lipid bilayer vesicles that were first prepared in the
1960sLiposomes can be seen as the simplest artificial biological cells,
which have potential applications in drug delivery, gene therapy and
artificial blood, as well as being used as a model of biological cell and cell
membrane. Liposomes are usually composed of phospholipids or
cholesterol, which are used to encapsulate various active drugs.
16. Nanopharmacology of liposomes
Liposomes may vary in size; most are 200 nm or smaller – these can
be termed ‘nanoliposomes’. However, there is a size limitation for
liposomes. Liposomal formulation is similar to that of a small section
of a circular lipid bilayer. During the formulation process, it must
sacrifice its edge energy in order to overcome the bending resistance;
thus, liposomes cannot be made as small as would be desired. If the
circular section of bilayer is too small, it would not have enough edge
energy to provide the necessary bending energy Liposomes are a
promising dosage form/drug delivery system owing to their size,
hydrophobic and hydrophilic character, biocompatibility,
biodegradability, low toxicity and immunogenicity
18. Nanopharmacology of liposomes
“...various liposomes are being intensively developed as
nanoformulations and have been shown to considerably
reduce the toxicity of anticancer drugs with significant
efficacy.”
19. Nanopharmacology of liposomes
From a nanopharmacological view, by entering directly into the
central compartment and distributing the drug to cancer tissues,
liposomal cancer therapies represent an additional compartment model
in the pharmacokinetic model. However, the tissue distribution
patterns are dependent on the type of liposome formulation. Generally,
the maximum amount of drug is rapidly released from liposomes into
the central compartment for therapy, before the liposomes are cleared by
the mononuclear phagocyte system. Surface modification of liposomes
slows mononuclear phagocyte system uptake, thereby retaining drug-
loaded liposomes in the plasma and enabling prolonged circulation,
extravasation in tissues, preferential uptake at the endothelium and
subsequent drug release in the tissue compartment
20. Niosomes
• Niosomes, non-ionic surfactant vesicles, are widely studied as
an alternative to liposomes
• These vesicles appear to be similar to liposomes in terms of
their physical properties
• They are also prepared in the same way and under a variety of
conditions, from unilamellar or multilamellar structures.
• Niosomes alleviate the disadvantages associated with
liposomes, such as chemical instability, variable purity of
phospholipids and high cost.
• They have the potential for controlled and targated drug delivery
• Niosomes enhanced the penetration of drugs
22. Nanopharmacology of Emulsions
Emulsions comprise oil in water-type mixtures that
are stabilized with surfactants to maintain size
and shape. The lipophilic material can be dissolved
in a water organic solvent that is emulsified in an
aqueous phase. Like liposomes, emulsions have been
used for improving the efficacy and safety of
diverse compounds
23. Nanopharmacology of Polymers
Polymers such as polysaccharide chitosan nanoparticles
have been used for some time now as drug delivery systems.
Recently, water-soluble polymer hybrid constructs have been
developed. These are polymer–protein conjugates or polymer–
drug conjugates.Polymer conjugation to proteins reduces
immunogenicity, prolongs plasma half-life and enhances
protein stability.Polymer–drug conjugation promotes
tumour targeting through the enhanced permeability and
retention effect and, at the cellular level following endocytic
capture,allows lysosomotropic drug delivery
24. Nanopharmacology of Ceramic
Ceramic nanoparticles are inorganic systems with porous
characteristics that have recently emerged as drug vehicles.
These vehicles are biocompatible ceramic nanoparticles such
as silica, titania and alumina that can be used in cancer
therapy. However, one of the main concerns is that these
particles are non-biodegradable, as they can accumulate in
the body, thus causing undesirable effects.
25. Nanopharmacology of Metallic
Metallic particles such as iron oxide nanoparticles (15–60
nm) generally comprise a class of superparamagnetic
agents that can be coated with dextran, phospholipids or other
compounds to inhibit aggregation and enhance stability.
The particles are used as passive or active targeting agents
26. Nanopharmacology of Gold shell
Gold shell nanoparticles, other metal-based agents, are a
novel category of spherical nanoparticles consisting of a
dielectric core covered by a thin metallic shell, which is
typically gold. These particles possess highly favourable
optical and chemical properties for biomedical imaging and
therapeutic applications
27. Nanopharmacology of Carbon
nanomaterials
Carbon nanomaterials include fullerenes and nanotubes. Fullerenes are
novel carbon allotrope with a polygonal structure made up exclusively by
60 carbon atoms. These nanoparticles are characterized by having
numerous points of attachment whose surfaces also can be
functionalized for tissue bindingNanotubes have been one of the most
extensively used types of nanoparticles because of their high electrical
conductivity and excellent strength. Carbon nanotubes can be
structurally visualized as a single sheet of graphite rolled to form a
seamless cylinder. There are two classes of carbon nanotubes: single-
walled (SWCNT) and multi-walled (MWCNT). MWCNT are larger and
consist of many single-walled tubes stacked one inside the other.
Functionalized carbon nanotubes are emerging as novel components in
nanoformulations for the delivery of therapeutic molecules
28. Nanopharmacology of Quantum
dots
Quantum dots are nanoparticles made of
semiconductor materials with fluorescent properties.
Crucial for biological applications quantum dots
must be covered with other materials allowing
dispersion and preventing leaking of the toxic
heavy metals
31. Larger diameter nanoshells used for Imaging
Smaller diameter nanoshells used for photothermal therapy applications
120 nm radius and 35 nm shell thickness 100 nm radius and 20 nm shell thickness
60 nm radius and 10 nm shell
Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer, Christopher Loo, B.S.1, Alex Lin, B.S.1, Leon Hirsch, B.S.1,Min-Ho Lee, M.S.1,Jennifer Barton, Ph.D.2,Naomi Halas,
Ph.D.3,JenniferWest, Ph.D.1,Rebekah Drezek, Ph.D.1
Images of Nanoshells
32. SOME SIGNIFICANT ACHIEVEMENTS OF
NANODEVICES
• Development of one dose a day ciprofloxacin
using nanotechnology
• Tumor targeted taxol delivery using nanoparticles
in Phase 2 clinical trial stage
• Improved ophthalmic delivery formulation using
smart hydrogel nanoparticles
• Oral insulin formulation using nanoparticles
carriers.
• Liposomal based Amphotericin B formulation
34. Nanotherapies
This decade will see the continued emergence of
nanotherapies for the diagnosis and treatment of cancer and
neurological disorders. Nanodrugs and delivery systems
offer incredible opportunities in the prevention, diagnosis,
and treatment of cardiovascular, pulmonary, and endocrine
diseases as well as those of dermatology and orthopedics.
Perhaps very soon, large doses of antibiotics will no longer
need to be prescribed for infections to overcome drug
decomposition in the gut and decolonization of the sinuses,
intestines, and vagina with many undesirable adverse
effects.
36. Nanotherapies
Nanochemotherapy designed based on biopsy
results and engineered to discern and ignore
healthy cells and target diseased cells
eliminates the systemic adverse effects of
treatment. Nanorobots, inhaled or injected,
could monitor responses to therapy, complete
cellular repairs, detect disease, or deliver
specific agents at specific targets
37. Nanotherapies
As sensitivity and specificity increase in
detection and monitoring, nanotechnology will
certainly change the way disease is defined and
treated.
Vaccines, eye treatments, patient monitoring,
and regenerative therapies will also undergo
significant transformation. Particularly exciting are
proposed nano solutions to diabetes using inhaled
biochips that continuously monitor glucose and
release insulin in precise doses to control glucose
levels
38. Nanotherapies
SAVE AND UNEASY SIDE OF NANOTECHNOLOGY
• Precision prescribing, smaller doses, and perhaps fewer adverse
effects make nanopharmacology so attractive
• Nanodrugs promise improved bioavailability, reduced toxicity,
and enhanced solubility, there is risk, and most of the risks is
unknown. Because nanodrugs and nanodevices cross the blood-
brain barrier and enter cellular environments so easily, many
risks of drug therapy may be intensified.
• Nanotechnology is an established discipline, nanomedicine and
nanonursing
39. Nanotherapies
SAVE AND UNEASY SIDE OF NANOTECHNOLOGY
Like all advances in healthcare, the science is preceding
the ethics. As nanotechnology integrates into practice,
many ethical and pragmatic issues will be addressed.
Table describes some of these issues for now and in the
future
43. Nanomedicine - Conclusion
• Nanotechnology will radically change the way we diagnose,
treat and prevent cancer
• Nanomedicine for cancer has the ability to improve health care
dramatically
• Current research is mostly in diagnostic tools, although there
are many other application of nanomaterials in medicine…
• There are still lots of advances needed to improve Nanomedicine
44. Nanopharmacology: an application of nanotechnology to the development and
discovery of drug delivery methods.
Summary
The idea of using nanoparticles to enhance efficacy of diagnostic and
therapeutic drugs is based on the fact that nanoscale substances have
properties distinct from those of substances in the macrodispersed form. In
particular, due to the high specific surface area of nanomaterials, surface
phenomena (adsorption, desorption and adhesion ) become predominant in their
interaction with macromolecules or biological objects. As a result, nanoparticles
may have high therapeutic efficacy without significant side effects at low
concentration. Certain nanostructures, both biogenic (viral particles,
capsids) and non-biogenic, are organised as a container, making them very
useful for the delivery of therapeutic or diagnostic compounds (including
other nanoparticles) to target cells or tissues. Specific antibodies, aptamers,
receptors or specific targeting ligands provide targeted delivery of
nanostructures. Nanoparticles may be used for imaging (e.g., in vivo diagnostics)
in nuclear magnetic resonance (magnetic particles), plasmon resonance
(nanoparticles of metals) and for the detection of fluorescence of both non-
biogenic (e.g., quantum dots) and biogenic (e.g., green fluorescent protein)
origin. Not all properties of nanodrugs that determine their pharmacokinetics, i.e.
absorption, distribution in tissues, biotransformation and excretion, have been
explored in full. A systematic study of nanomedicines is necessary to identify
their treatment capabilities and possible health hazards.
45. Nanotoxicology
Although humans have been exposed to airborne nanosized
particles (NSPs; < 100 nm) throughout their evolutionary stages,
such exposure has increased dramatically over the last century due
to anthropogenic sources. The rapidly developing field of
nanotechnology is likely to become yet another source through
inhalation, ingestion, skin uptake, and injection of engineered
nanomaterials. Information about safety and potential hazards is
urgently needed. Results of older biokinetic studies with NSPs and
newer epidemiologic and toxicologic studies with airborne ultrafine
particles can be viewed as the basis for the expanding field of
nanotoxicology, which can be defined as safety evaluation of
engineered nanostructures and nanodevices.
46. Nanotoxicology
some emerging concepts of nanotoxicology can be identified from
the results of these studies. When inhaled, specific sizes of NSPs
are efficiently deposited by diffusional mechanisms in all regions
of the respiratory tract. The small size facilitates uptake into cells
and transcytosis across epithelial and endothelial cells into the
blood and lymph circulation to reach potentially sensitive target
sites such as bone marrow, lymph nodes, spleen, and heart. Access
to the central nervous system and ganglia via translocation along
axons and dendrites of neurons has also been observed
47. Nanotoxicology
NSPs penetrating the skin distribute via uptake into lymphatic
channels. Endocytosis and biokinetics are largely dependent on
NSP surface chemistry (coating) and in vivo surface
modifications. The greater surface area per mass compared with
larger-sized particles of the same chemistry renders NSPs more
active biologically. This activity includes a potential for
inflammatory and pro-oxidant, but also antioxidant, activity,
which can explain early findings showing mixed results in terms
of toxicity of NSPs to environmentally relevant species. Evidence of
mitochondrial distribution and oxidative stress response after NSP
endocytosis points to a need for basic research on their interactions
with subcellular structures.
48. Nanotoxicology
Additional considerations for assessing safety of engineered NSPs
include careful selections of appropriate and relevant
doses/concentrations, the likelihood of increased effects in a
compromised organism, and also the benefits of possible desirable
effects. An interdisciplinary team approach (e.g., toxicology,
materials science, medicine, molecular biology, and bioinformatics,
to name a few) is mandatory for nanotoxicology research to arrive
at an appropriate risk assessment.