Hitesh R. Patel
Mr. Rajeev Garg
A nanoparticle is a microscopic particle whose size is measured in nanometres (nm). It is defined as a particle with at least one dimension <200nm.or nanoparticles are solid colloidal particles ranging in size from 10nm to 1000nm. They consist of macromolecular materials in which the active principle is dissolved, entrapped or encapsulated, and/or to which the active principle is absorbed or attached.1
Nanoparticles (NP) have been studied extensively as particulate carriers in several pharmaceutical and medical fields. Nanoparticles, in general, can be used to provide targeted(cellular/tissue) delivery of drugs, to sustain drug effect in target tissue,2 to improve oral bioavailability to solubilize drugs for intra-vascular delivery and to improve the stability of therapeutic agents against enzymatic degradation.
Nanoparticle can be formulated, as injections consisting of spherical amorphous particles which do not aggregate, hence they can be safely administered by the intravenous route. Since no cosolvent is used to solubilize the drug, the overall toxicity of the formulation is decreased.
Nanoparticles represent very promising carrier system for the targeting of anti-cancer agents to tumors. Nanoparticles exhibit a significant tendency to accumulate in a number of tumors after iv injection. Nanoparticles can also be used in Brain Drug Targeting.Poly (butyl cyanoacrylate) nanoparticles represent the only nanoparticles that were so far successfully used for in vivo delivery of drugs to brain. This polymer has the advantage that it is very rapidly biodegradable.The first drug that was delivered to brain using nanoparticles was the Hexapeptide Dalargin (Tyr-D-Ala-Gly-Phe-Leu-Arg), a Leu-enkephalin analouge with opioid activity.3 Other drugs that have successfully been transported into the brain are loperamide, tubocurarine, and doxorubicin.Nanoparticles mediated drug transport to the brain depends on the overcoating of the particles with polysorbates, especially polysorbate 80.
The factors that govern the permeation of a drug across the normal BBB and determine its time dependent concentration within the brain following its systemic administration include the following:-
Nanoparticles hold promise for the targeted delivery of drugs to inflammed areas of the body after administration by a number of possible routes.They have been investigated for lymphatic targeting also.Nanocapsules may have potential to deliver drugs to the lymph node through tissue spaces by local administration.
The cosmetic applications of nanoparticles are currently under investigation.A cosmetic product containing nanocapsules of VitaminE PrimordialeR is recently launched.
Natural or synthetic polymer
Particle diameter <100nm
No platelet aggregation
Prolonged circulation time
Solid Lipid Quantum Nanoparticles (SLN)
A quantum dot is a semiconductor nanostructure that confines the motion of conduction band electrons, valence band holes, or excitons (pairs of conduction band electrons and valence band holes) in all three spatial directions. The confinement can be due to electrostatic potentials (generated by external electrodes, doping, strain, impurities), due to the presence of an interface between different semiconductor materials (e.g. in the case of self-assembled quantum dots), due to the presence of the semiconductor surface (e.g. in the case of a semiconductor nanocrystal), or to a combination of these. A quantum dot has a discrete quantized energy spectrum.. A quantum dot4 contains a small integer number (of the order of 1-100) of conduction band electrons, valence band holes, or excitons, i.e., an integer number of elementary electric charges.5
Small quantum dots, such as colloidal semiconductor nanocrystals, can be as small as 2 to 10 nanometers, corresponding to 10 to 50 atoms in diameter and a total of 100 to 100'000 atoms within the quantum dot volume. Self-assembled quantum dots are typically between 10 and 50 nanometers in size. Quantum dots defined by lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in semiconductor heterostructures can have lateral dimensions exceeding 100 nanometers6. At 10 nanometers in diameter, nearly 3 million quantum dots could be lined up end to end and fit within the width of a human thumb.
Quantum dots can be contrasted to other semiconductor nanostructures:
1) quantum wires, which confine the motion of electrons or holes in two spatial directions and allow free propagation in the third.
2) quantum wells, which confine the motion of electrons or hles in one direction and allow free propagation in two directions.
Quantum dots with a nearly spherical symmetry, or flat quantum dots with nearly cylindrical symmetry can show shell filling according to the equivalent of Hund's rules for atoms. Such dots are sometimes called "artificial atoms". In contrast to atoms, the energy spectrum of a quantum dot can be engineered by controlling the geometrical size, shape, and the strength of the confinement potential.
Like in atoms, the energy levels of small quantum dots can be probed by optical spectroscopy techniques. In quantum dots that confine electrons and holes, the interband absorption edge is blue shifted due to the confinement compared to the bulk material of the host semiconductor material. As a consequence, quantum dots of the same material, but with different sizes, can emit light of different colors.6,7
Quantum dots are particularly significant for optical applications due to their theoretically high quantum yield. In electronic applications they have been proven to operate like a single-electron transistor and show the Coulomb blockade effect. Quantum dots have also been suggested as implementations of qubits for quantum information processing.
Researchers at Los Alamos National Laboratory have developed a wireless nanodevice that efficiently produces visible light, through energy transfer from nano-thin layers of quantum wells to nanocrystals above the nanolayers.
Quantum dots are one of the most hopeful candidates for solid-state quantum computation. By applying small voltages to the leads, one can control the flow of electrons through the quantum dot and thereby make precise measurements of the spin and other properties therein.
Another cutting edge application of quantum dots is also being researched as potential artificial fluorophore for intra-operative detection of tumors using fluorescence spectroscopy
Nanocrystalline silicon (nc-Si) - an allotropic form of silicon - is similar to amorphous silicon (a-Si), in that it has an amorphous phase. Where they differ, however, is that nc-Si has small grains of crystalline silicon within the amorphous phase. This is in contrast to polycrystalline silicon (poly-Si) which consists solely of crystalline silicon grains, separated by grain boundaries. nc-Si is sometimes also known as microcrystalline silicon (µc-Si)8 The difference comes solely from the grain size of the crystalline grains. Most materials with grains in the micrometre range are actually fine-grained polysilicon, so nanocrystalline silicon is a better term.
nc-Si has many useful advantages over a-Si, one being that if grown properly it can have a higher mobility, due to the presence of the silicon crystallites.9 It also shows increased absorption in the red and infrared wavelengths, which make it an important material for use in a-Si solar cells. One of the most important advantages of nanocrystalline silicon, however, is that it has increased stability over a-Si, one of the reasons being because of its lower hydrogen concentration.
Although it currently cannot attain the mobility that poly-Si can, it has the advantage over poly-Si that it is easier to fabricate, as it can be deposited using conventional low temperature a-Si deposition techniques, such as PECVD, as opposed to laser annealing or high temperature CVD processes, in the case of poly-Si.10
Photonic crystals are periodic dielectric or metallo-dielectric (nano)structures that are designed to affect the propagation of electromagnetic waves (EM) in the same way as the periodic potential in a semiconductor crystal affects the electron motion by defining allowed and forbidden electronic energy bands.
The absence of allowed propagating EM modes inside the structures, in a range of wavelengths called a photonic band gap, gives rise to distinct optical phenomena such as inhibition of spontaneous emission, high-reflecting omnidirectional mirrors and low-loss-waveguiding among others.11,12
Since the basic physical phenomenon is based on diffraction, the periodicity of the photonic crystal structure has to be in the same length-scale as half the wavelength of the EM waves i.e. ~300 nm for photonic crystals operating in the visible part of the spectrum. This makes the synthesis cumbersome and complex. To circumvent nanotechnological methods with their big and complex machinery, different approaches have been followed to grow photonic crystals as self-assembled structures from colloidal crystals.
Photonic crystals are attractive optical materials for controlling and manipulating the flow of light. They are of great interest for both fundamental and applied research, and are expected to find commercial applications soon.
Two-dimensionally periodic photonic crystals already have reached a level where integrated-device applications are in sight, whereas their three-dimensional counterparts are still far from commercialization but will offer additional advantages possibly leading to new device concepts, when some technological aspects such as manufacturability and principal difficulties such as disorder are under control.
The first commercial products involving two-dimensionally periodic photonic crystals are already available in the form of photonic-crystal fibers, which use a nanoscale structure to confine light with radically different characteristics compared to conventional optical fiber for applications in nonlinear devices, guiding exotic wavelengths, and so on.13
A liposome is a spherical vesicle with a membrane composed of a phospholipid bilayer used to deliver drugs or genetic material into a cell. Liposomes can be composed of naturally-derived phospholipids with mixed lipid chains (like egg, phosphatidylethanolamine), or of pure components like DOPE (dioleolylphosphatidylethanolamine).
The lipid bilayer can fuse with other bilayers (e.g., the cell membrane), thus delivering the liposome contents. By making liposomes in a solution of DNA or drugs,(which would normally be unable to diffuse through the membrane), they can be (indiscriminately) delivered past the lipid bilayer.
The use of liposomes for transformation or transfection of DNA into a host cell is known as lipofection.Liposomes can be created by sonicating phospholipids in water.14
In an effort to improve bioavailability anti-H.pylori effects of antibiotics, mucoadhesive gliadin nanoparticles (GNP) which have the ability to deliver the antibiotics at the sites of infection were prepared. GNP bearing clarithromycin(CGNP) and omeprazole(OGNP) were prepared by desolvation method.
In vivo gastric mucoadhesive studies confirmed the strong mucoadhesive propensity and specificity and specificity of gliadin nanoparticles towards stomach. Gliadin nanoparticles show a higher tropism for the gastrointestinal regions and their presence in other intestinal regions is very low. This high capacity to interact with the mucosa may be explained by gliadin composition15.
In fact, this protein is rich in neutral and lipophilic residues. Neutral amino acid can promote hydrogen bonding interaction with the mucosa whereas the lipophilic components can interact within biological tissue by hydrophilic interaction. The related protein gliadin possessing an amino and disulphide groups on the side chain has a good probability of developing bonds with mucin gel.
Polymeric nanoparticles have been invented by Speiser et al. They represent interesting alternative as drug delivery systems to liposomes.They usually exhibit a long shelf life and a good stability on storage.
.These are superior to liposomes in targeting them to specific organs or tissues by adsorbing and coating their surface with different substances.
Nanoparticles can be prepared either from preformed polymers, such as polyesters (i.e. polylactic acid), or from a monomer during its polymerization, as in the case of alkyl-cyanoacrylates
.Most of the methods based on the polymerization of monomers consists in adding a monomer into the dispersed phase of an emulsion, an inverse microemulsion, or dissolved in a non-solvent of the polymer.16
Solid lipid nanoparticles have been developed as alternative delivery system to conventional polymeric nanoparticles.SLNs are sub-micron colloidal carriers
(50-1000nm) which are composed of physiological lipid, dispersed in water or in an aqueous surfactant solution.15,16
SLNs combine advantages of polymeric nanoparticles, fat emulsions and liposomes, but avoid some of their disadvantages.They are biodegradable, biocompatible and non-toxic.
Avoidance of coalescence leads to enhanced physical stability.
Reduced mobility of incorporated drug molecules leads to reduction of drug leakage.
Static interface solid/liquid facilitates surface modification.17
Gold nanoparticles stabilized by thiol functionality are extraordinarily stable and therefore are a great system for studying nanostructure formation. They have many applications17. Because gold nanoparticles are so easy to synthesize they have been studied intensely in recent years.
A common synthesis involves the reduction of a gold salt in the presence of capping agent molecules such as thiols, citrates or phosphines. The functionalities of these capping agents can be altered to yield various chemical properties.
The synthesis of gold nanoparticles with a polymer-thiol monolayer involves the the mechanism of particle formation in the presence of bulky ligands. TEM has been used extensively as a way of characterizing the particles. Figure shows an example of TEM imaged particles.18
Binding gold nanoparticles to a specific antibody for cancer cells could make cancer detection19 much easier,.
Gold nanoparticles stick to cancer cells and make them shine.
“Gold nanoparticles are very good at scattering and absorbing light.
Many cancer cells have a protein, known as Epidermal Growth Factor Receptor (EFGR), all over their surface.By conjugating, or binding, the gold nanoparticles to an antibody for EFGR, suitably named anti-EFGR, researchers were able to get the nanoparticles to attach themselves to cancer cells.
Gold nanoparticles don’t stick as well to noncancerous cells. The results can be seen with a simple microscope.In the study, researchers found that the gold nanoparticles have 600 percent greater affinity for cancer cells than for noncancerous cells. The particles that worked the best were 35 nanometers in size. Researchers tested their technique using cell cultures of two different types of oral cancer and one nonmalignant cell line. The shape of the strong absorption spectrum of the gold nanoparticles are also found to distinguish between cancer cells and noncancerous cells.19
Nanoparticle characterization20 is necessary to establish understanding and control of nanoparticle synthesis and applicationsThe primary characterisation of NPs is the size of the newly formed particles.
Particles with a very small size (<1000nm), low charge, and a hydrophilic surface are not recognised by the mononuclear phagocytic system(MPS) and, therefore, have a long half life in the blood circulation which is essential for targeting NPs to target brain.
Characterization is done by using a variety of different techniques, mainly drawn from materials science.
Electron microscopy [TEM,SEM]
Atomic force microscopy [AFM]
Dynamic light scattering [DLM]
X-ray photoelectron spectroscopy [XPS]
Powder x-ray diffractometry [XRD]
With nanotechnology, a large set of materials with distinct properties (optical, electrical, or magnetic) can be fabricated. Nanotechnologically improved products rely on a change in the physical properties when the feature sizes are shrunk. Nanoparticles for example take advantage of their dramatically increased surface area to volume ratio. Their optical properties, e.g. fluorescence, become a function of the particle diameter. When brought into a bulk material, nanoparticles can strongly influence the mechanical properties, such as the stiffness or elasticity. Example, traditional polymers can be reinforced by nanoparticles resulting in novel materials e.g. as lightweight replacements for metals. Therefore, an increasing societal benefit of such nanoparticles can be expected.
The biological and medical research communities have exploited the unique properties of nanomaterials for various applications (e.g., contrast agents for cell imaging and therapeutics for treating cancer). Terms such as biomedical nanotechnology, bionanotechnology, and nanomedicine are used to describe this hybrid field.Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications.Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug-delivery vehicles.
Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Biological tests measuring the presence or activity of selected substances become quicker, more sensitive and more flexible when certain nanoscale particles are put to work as tags or labels. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. Gold nanoparticles, tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots, into polymeric microbeads. Nanopore technology foranalysis of nucleic acids converts strings of nucleotides directly into electronic signatures.
The overall drug consumption and side-effects can be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. This highly selective approach reduces costs and human suffering. An example can be found in dendrimers and nanoporous materials. They could hold small drug molecules transporting them to the desired location. Another vision is based on small electromechanical systems: NEMS are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells.A targeted or personalized medicine reduces the drug consumption and treatment expenses resulting in an overall societal benefit by reducing the costs to the public health system.
Nanotechnology can help to reproduce or to repair damaged tissue. This so called “tissue engineering” makes use of artificially stimulated cell proliferation by using suitable nanomaterial-based scaffolds and growth factors. Tissue engineering might replace today’s conventional treatments, e.g. transplantation of organs or artificial implants. On the other hand, tissue engineering is closely related to the ethical debate on human stem cells and its ethical implications.
Chemical catalysis and filtration techniques are two prominent examples where nanotechnology already plays a role. The synthesis provides novel materials with tailored features and chemical properties e.g. nanoparticles with a distinct chemical surrounding (ligands) or specific optical properties. In this sense, chemistry is indeed a basic nanoscience. In a short-term perspective, chemistry will provide novel “nanomaterials” and in the long run, superior processes such as “self-assembly” will enable energy and time preserving strategies.In a sense, all chemical synthesis can be understood in terms of nanotechnology, because of its ability to manufacture certain molecules. Thus, chemistry forms a base for nanotechnology providing tailor-made molecules, polymers etc. and furthermore clusters and nanoparticles.
A strong influence of nanochemistry on waste-water treatment, air purification and energy storage devices is to be expected. Mechanical or chemical methods can be used for effective filtration techniques. One class of filtration techniques is based on the use of membranes with suitable hole sizes, whereby the liquid is pressed through the membrane. Nanoporous membranes are suitable for a mechanical filtration with extremely small pores smaller than 10 nm (“nanofiltration”). Nanofiltration is mainly used for the removal of ions or the separation of different fluids. On a larger scale, the membrane filtration technique is named ultrafiltration, which works down to between 10 and 100 nm. One important field of application for ultrafiltration is medical purposes as can be found in renal dialysis.
Magnetic nanoparticles offer an effective and reliable method to remove heavy metal contaminants from waste water by making use of magnetic separation techniques. Using nanoscale particles increases the efficiency to absorb the contaminants and is comparatively inexpensive compared to traditional precipitation and filtration methods.
The most advanced nanotechnology projects related to energy are: storage, conversion, manufacturing improvements by reducing materials and process rates, energy saving e.g. by better thermal insulation, and enhanced renewable energy sources.
A reduction of energy consumption can be reached by better insulation systems, by the use of more efficient lighting or combustion systems, and by use of lighter and stronger materials in the transportation sector. Currently used light bulbs only convert approximately 5% of the electrical energy into light. Nanotechnological approaches like light-emitting diodes (LEDs) or quantum caged atoms (QCAs) could lead to a strong reduction of energy consumption for illumination.
Because of the relatively low energy density of batteries the operating time is limited and a replacement or recharging is needed. The huge number of spent batteries and accumulators represent a disposal problem. The use of batteries with higher energy content or the use of rechargeable batteries or supercapacitors with higher rate of recharging using nanomaterials could be helpful for the battery disposal problem.
Current high-technology production processes are based on traditional top down strategies, where nanotechnology has already been introduced silently. The critical length scale of integrated circuits is already at the nanoscale (50 nm and below) regarding the gate length of transistors in CPUs or DRAM devices.
An example of such novel devices is based on spintronics. The dependence of the resistance of a material (due to the spin of the electrons) on an external field is called magnetoresistance. This effect can be significantly amplified (GMR - Giant Magneto-Resistance) for nanosized objects, for example when two ferromagnetic layers are separated by a nonmagnetic layer, which is several nanometers thick (e.g. Co-Cu-Co).
The GMR effect has led to a strong increase in the data storage density of hard disks and made the gigabyte range possible. The so called tunneling magnetoresistance (TMR) is very similar to GMR and based on the spin dependent tunneling of electrons through adjacent ferromagnetic layers.
Both GMR and TMR effects can be used to create a non-volatile main memory for computers, such as the so called magnetic random access memory or MRAM.
In the modern communication technology traditional analog electrical devices are increasingly replaced by optical or optoelectronic devices due to their enormous bandwidth and capacity, respectively. Two promising examples are photonic crystals and quantum dots .
Photonic crystals are materials with a periodic variation in the refractive index with a lattice constant that is half the wavelength of the light used. They offer a selectable band gap for the propagation of a certain wavelength, thus they resemble a semiconductor, but for light or photons instead of electrons.
Quantum dots are nanoscaled objects, which can be used, among many other things, for the construction of lasers. The advantage of a quantum dot laser over the traditional semiconductor laser is that their emitted wavelength depends on the diameter of the dot. Quantum dot lasers are cheaper and offer a higher beam quality than conventional laser diodes.
The production of displays with low energy consumption could be accomplished using carbon nanotubes (CNT). Carbon nanotubes can be electrically conductive and due to their small diameter of several nanometers, they can be used as field emitters with extremely high efficiency for field emission displays (FED). The principle of operation resembles that of the cathode ray tube, but on a much smaller length scale.
Numerous methods exits for the manufacture of nanoparticles, allowing extensive modulation of their structure, composition and physicochemical properties.The choice of preparation method essentially depends on the raw materials intended to be used and on the solubility characterstics of active compound to be associated with the particles.
Regarding raw material, criteria such as biocompatibility, the degradation behaviour, choice of administrative route, desired release profile of the drug and finally the type of biomedical application determine its selection.
NPs vary in types of polymers, stabilizers and surfactants used in their manufacturing process.When manufacturing NPs as drug carriers, in-vivo and in-vitro testing should consider the factors listed below.
The primary manufacturing methods of NPs from preformed polymers include:
a) Emulsion evaporation
b) Salting out
c) Solvent displacement
Furthermore, drug loading can be accomplished by absorption, adsorption and encapsulation.
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Dr. G. D. Gupta is working as a professor and principal in ASBASJSM College of Pharmacy, Bela, Ropar, India. Dr. Gupta has author of number of books and published more than 100 Research Paper / Abstract in National and International conferences.
Mr. Rajeev Garg is working a lecturer cum research scholar in department of pharmaceutics in ASBASJSM College of Pharmacy, Bela, Ropar, India. He had completed his graduation from Rameesh institutions, Greater Noida and post graduation from B.N.College of pharmacy, Udaipur, Raj. He has very good academic and extra circular record.
Shailesh Sharma is working a lecturer cum research scholar in department of pharmaceutics in ASBASJSM College of Pharmacy, Bela, Ropar, India.He had completed his graduation from B . R. Nahata College of pharmacy, Mandsaur, (MP) and post graduation from B.N.College of pharmacy, Udaipur, Raj. He has very good academic and extra circular record.
Mr. Rajneesh Kalia is a B.Pharm. final year student of ASBASJSM College of Pharmacy, Bela, Ropar, India.
Hitesh R. Patel
Since 1970, strategies to fight cancer have continued to change and improve.
The diagnosis and treatment of cancer have been greatly improved with the recent Developments in nanotechnology.
Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such
Cancer today is one of the leading causes of death. Though highly developed technologies for treatment prevail, this disease still remains a deadly one, claiming many lives. The failure of chemotherapy for treating cancer can be attributed to: 1. Low aqueous solubility of anti-cancer drugs. 2. Low permeability. This leads to poor accessibility of anti-neoplastic agents to the tumor. High doses are required which result in toxicity and heavy side-effects.
This led to a need to improve the drug delivery and bio-availability.
Knowledge from nanotechnology, advanced polymer chemistry and electronic engineering is now employed to design new targeted drug delivery systems which ensure maximum drug concentration at the tumor site, preventing damage to normal tissues and controlled delivery of the chemotherapeutic agents.
Cancer treatment using nanotechnology utilizes the phenomenon of targeted bioconjugate drug delivery system; wherein a biocompatible and biodegradable polymer nanoparticle encapsulates the anti-cancer drug and binds to an aptamer.
The aptamers are small DNA or RNA fragments which bind to target antigens with high specificity and high affinity: analogous to Monoclonal Antibodies. They have the potential to act as targeting molecules-directing the encapsulated nanoparticles to the tumor-antigens present on the surface of tumor cells.
Eg: In case of prostrate cancer, the RNA-aptamers are highly specific to PSMA [prostrate specific membrane antigen], and bind to it. The PSMA is a marker for prostrate cancer, over-expressed on prostrate epithelial cells.
Thus, the highly specific RNA-aptamer along with the therapeutic nanoparticles is a specially designed delivery system that allows a pre-determined and regulated release of drug at the tumor site.
Once bound to the cancer cells, the nanoparticle-aptamer bioconjugates are internalized making it possible for their cytotoxic payload to get released directly inside the cancer cells.
Quantum dots (QDs) are stable, bright fluorophores that, under ideal conditions, can have high quantum yields, narrow fluorescence emission bands
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