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

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 ) from individual atoms and molecules.

NANOTECHNOLOGY: PRODUCING OF NANOPARTICLES

Mechanical disintegration. Chemical synthesis. Photochemical synthesis. Vacuum evaporation methods. Microbiological synthesis.

 Metal-based nanoparticles Lipid-based nanoparticles Polymer-based nanoparticles

Biological nanoparticles

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.

Yes we are visit Nano

Thats Nanopharmacology

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 Theres Plenty of Room at the Bottom. He proposed to use a set of conventionalsized 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

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

Type of Nanoparticles 1 2 3 Polymeric Nanoparticles Quantum Dots Nanopores

Material Used Biodegradable Polymers CdSeCdS core-shell Aerogel, which is produced by solgel chemistry

Application Controlled and targeted drug delivery Targeting, Imaging Agent Controlled release drug carriers

4
5

Nanowires or CarbonNanotubes
Nanoshells coated with gold

Metals, semiconductors or carbon

Dielectric (typically gold sulfide or silica) core and a metal (gold) shell.

Gene and DNA delivery

Tumor Targeting Controlled and targeted drug delivery Drug targeting, Biomolecules delivery Systemic and controlled delivery of waterinsoluble drugs Controlled and targeted drug Delivery

6
7 8 9

Liposomes
Ceramic nanoparticles Polymeric micelles Polymeric Nanoparticles

Phospholipid Vesicles
Silica, alumina, titania Amphiphilic block copolymers Biodegradable Polymers

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

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

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

Drug Delivery Carriers

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.

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

Liposome's

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.

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

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

Niosomes

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

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 polymerprotein conjugates or polymer drug conjugates.Polymer conjugation to proteins reduces immunogenicity, prolongs plasma half-life and enhances protein stability.Polymerdrug conjugation promotes tumour targeting through the enhanced permeability and retention effect and, at the cellular level following endocytic capture,allows lysosomotropic drug delivery

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.

Nanopharmacology of Metallic
Metallic particles such as iron oxide nanoparticles (1560 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

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

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: singlewalled (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

Nanopharmacology of Carbon nanomaterials

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

Nanopharmacology of Quantum dots

Nanoparticles

Reference: Ed Neuwelt, Oregon Health Sciences University

Nanoshells

Reference: Jennifer West, Rice University

Images of Nanoshells
Larger diameter nanoshells used for Imaging

120 nm radius and 35 nm shell thickness

100 nm radius and 20 nm shell thickness

Smaller diameter nanoshells used for photothermal therapy applications

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

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

Nanotherapy
Advantages and Difficulties

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.

Nanotherapies
Shielding transplanted tissue from immune responses, disease detection, cell and vascular repair, and targeted gene and tissue therapy is just the beginning.

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

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

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 bloodbrain barrier and enter cellular environments so easily, many risks of drug therapy may be intensified. Nanotechnology is an established discipline, nanomedicine and nanonursing

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

Targeting Ligands

Nanomedicine and Cancer

Why Nanomedicine?
Virus Seeking Probes

Nanotechnology offers great advancements to medicine

There is still a lot to be learned about the human body and nanotechnology offers a lot of help.
Artery Cleaner

Source: http://science.nasa.gov/headlines/y2002/15jan_nano.htm

Nano-Robots Replacing Neurons

Source: http://www.e-spaces.com/Portfolio/trans/blood/index.html

Source: http://foresight.org/Nanomedicine/Gallery/index.html

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

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 nonbiogenic (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.

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.

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

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.

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.