Applications to drugs and other molecules
A significant amount of work using nanotechnological approaches to crossing the BBB has focused on the delivery of antineoplastic drugs to CNS tumors. For example, radiolabeled polyethylene glycol (PEG)-coated hexadecylcyanoarcylate nanospheres have been tested for their ability to target and accumulate in a rat model of gliosarcoma [1]. Another group has encapsulated the antineoplasitc drug paclitaxel in polylactic co-glycolic acid nanoparticles, with impressive results. In vitro experiments with 29 different cancer cell lines (including both neural and non-neural cell lines) demonstrated targeted cytotoxicity 13 times greater than with drug alone [2]. Using a variety of physical and chemical characterization methods, including different forms of spectroscopy and atomic force microscopy, the investigators showed that the drug was taken up by the nanoparticles with very high encapsulation efficiencies and that the release kinetics could be carefully controlled. Research focusing on the delivery of many of the commonly used antineoplastic drugs is important because most of these drugs have poor solubility under physiologic conditions and require less than optimal vehicles, which can produce significant side effects.

The delivery of other drugs is also being investigated. Dalargin is a hexapeptide analog of leucine-enkephalin containing D-alanine, which produces CNS analgesia when it is delivered intracerebroventricularly, but it has no analgesic effects if it is administered systemically, specifically because it cannot cross the BBB on its own .[3H]Dalargin was conjugated to the same poly(butylcyanoacrylate) nanoparticles described above, injected systemically into mice, and demonstrated by radiolabeling to cross the BBB and accumulate in brain .Other, similar studies have also demonstrated delivery of dalargin using polysorbate 80-coated nanoparticles .Other polysorbate 80 nanoparticles have been chemically conjugated to the hydrophilic drug diminazenediaceturate (diminazene) and proposed as a novel treatment approach for second stage African trypanosomiasis .In other work, PEG-treated polyalkylcyanoacrylate nanoparticles were shown to cross the BBB and accumulate at high densities in the brain in experimental autoimmune encephalomyelitis, a model of multiple sclerosis. (11)

5. Gold nanoparticles help earlier diagnosis of liver cancer

Cancer spotters A new diagnostic technique can spot tumor-like masses as small as 5 millimeters in the liver. Gold nanoparticles with a polyelectrolyte coating can make smaller tumors more visible through X-ray scatter imaging, enabling earlier diagnosis.(12)

Applications and potential benefits
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.

1. Medicine
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.

2. Diagnostics
Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Biological tests 1measuring 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.

3. Drug delivery
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.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.

4. Tissue engineering
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.

5. Chemistry and environment
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.

6. Filtration
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.

7. Energy
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.

8. Reduction of energy consumption
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.

9. Recycling of batteries
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.

10. Information and communication
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.

11. Novel semiconductor 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.


SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email