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Future of nanotechnology in pharma industry
Medha Joshi & Vandana Patravale | Thursday, November 26, 2009, 08:00 Hrs  [IST]

Nanotechnology is the latest scientific trend along with other emerging technologies like biotechnology, genetic engineering, tissue engineering, gene therapy, combinatorial chemistry, high throughput screening, and stem cells. The presence of nanotechnology is now being felt in various industries including information technology, national defence, consumer goods, sustainable energy generation and medicine. It is slowly revolutionizing each of these fields.

According to national nanotechnology initiatives’ (NNI) definition of nanotechnology is the creation of functional materials, devices and systems, through the understanding and control of matter at dimensions in the nanometre scale length (1-100 nm), where new functionalities and properties of matter are observed and harnessed for a broad range of applications. Encompassing nanoscale science, engineering and technology, nanotechnology involves imaging, measuring, modelling, and manipulating matter at this length scale. Nanotechnology is unique in that it represents not just one specific area, but a vast variety of disciplines ranging from basic material science to personal care applications.

In 1959, physicist and Nobel prize winner Richard Feynman gave a lecture to the American Physical Society called "There's Plenty of Room at the Bottom." The focus of his speech was about the field of miniaturization and how he believed man would create increasingly smaller, powerful devices. In 1986, K. Eric Drexler wrote "Engines of Creation" and introduced the term nanotechnology. Scientific research has really expanded over from then to the last decade and inventors and corporations aren't far behind -- today, more than 13,000 patents registered with the US Patent Office have the word "nano" in them. According to Espicom Healthcare Intelligence report by 2018, the nanotechnology market in pharmaceutical industry can exceed US $13 billion. The market will mature as the number of marketed nano-enabled products doubles and second generation nanomedicines begin to emerge. These agents will address areas of high unmet clinical need and result in the formulation of approved and novel drugs which are safer, less toxic and more efficacious than first generation products.

Currently, application of nanotechnology in pharma industry is mainly in the three areas viz. drug discovery i.e. drug research and development, diagnostics and imaging and drug delivery. The utility of nanotechnology in the area of drug discovery i.e.. drug research and development is mainly in the field of nanofluidics and nanosensors, which allow chemical reactions to occur at nano scale. This offers speed, accuracy and number of reactions can be carried out at one time. Examples of processes that benefit from programmable nanofluidics include dynamic determination of dose-response curves, reactions at fixed pH, stoichiometric reactions, compound library cherry picking, trial-and-error protocols. Examples include Nanosys®, a ultraminiature nanoarrays for biomolecular analysis and Symyx®, a high throughput screening of thousands of materials for use in various products and biomedical devices.

In the area of imaging and diagnostics nanotechnology has done wonders by providing the virtues of sensitivity, accuracy in detection especially in the early stages of the diseases like cancer. Because of this the popularity of diagnostic agents in nanocarriers is increasing day by day. The area of diagnostics is also benefited with the advent of nanosensors, nanoarrays and quantum dots which add up in sensitive determination of reaction end points. Quantum dots can be tracked very precisely when molecules are “bar-coded” by their unique light spectrum, which makes them extremely useful in diagnostics. The examples of nano carrierrr based contrast agents include Lumirem®, Endorem®, Gadomer®. In India, the Central Scientific Instruments Organisation (CSIO) has completed simulation and design parameters for a micro-diagnostic kit for tuberculosis using nanotechnology. The kit uses the principle of nanosized biosensors.

The major chunk of application of nanotechnology is in drug delivery. Nanomedicine is the term that describes application of nanotechnology in medicine mainly in the areas of drug delivery system, new therapies, in vivo imaging, cell repair systems, implants, in vitro diagnostics and biomaterials. The size measurements are bit relaxed for clinically useful nano medicinee which might range from true nanosytemse.g.g drug–polymer conjugates and polymer micelles to micro particles in the range of 100 µm.

The various advantages offered by nanotechnology to nanomedicines are improved solubility, requirement of small doses, avoidance of side effects, enhanced biocompatibility and bioavailability, ability to entrap lipophilic as well as hydrophilic drugs, amenable to be delivered through various routes of administration, protection from degradation, longer residence times and reduced dosage frequency, extreme versatility: designed to elicit the desired kinetics, uptake, and response from the body. Nanotechnology could be an apt way to manage pharmaceutical life span of blockbuster drugs.

The potentials applications are listed below:
Tissue specific delivery - targeting the delivery of small and macro molecules across biological membranes such as the blood brain barrier for CNS drugs;e.g...... Mylotarg® by Wyeth is a gemtuzumab ozogamicin with targeting agent humanized anti-CD 33 antibody conjugated to a cytotoxic antitumor antibiotic, calicheamicin for treatment of cancer.

Gene and vaccine delivery - non-viral delivery of genetic materials in nanohydrogels and nanocarriers with a high degree of efficiency and expression; e.g. Lipofectamine® a liposome based transfection reagent by Invitrogen

Controlled-release devices - design of new nanoporous, bioerodible membranes; Increased biocompatibility - design of artificial surfaces engineering for medical and dental implants to by-pass unwanted inflammatory response as in stents e. g. Cypher® a sirolimus eluting coronary stent by Cordis, Taxus® a paclitaxel eluting coronary stent by Boston scientific

Improved drug bioavailability and solubility - through the engineering of drugs and reagents by nanostructuring e.g. Nanomorph™ by Soligs/Abbott, Nanocrystal™ by Élan Nanosystems, Dissocubes® by SkyePharma, Nanopure by PharmaSol ,NANOEDGE™ by Baxter

Before the term nanotechnology was coined, emulsion based drug delivery systems in nano range such as liposomes, polymer micelles, dendrimers, nanoparticles, nanocrystals and microparticles existed. In the transition period nano/micro fabrication techniques such as microchip systems, microneddle transdermal systems, layer by layer assembled systems and microdispensed particles were developed. Whereas in the future nano/micro manufacturing techniques such as nano/micro machines for scale up production will be on priority in the research. The day will not be far when soft gelatin capsules which are produced on centimeter scale now will be manufactured at nano/micro level. Nanotechnology can do wonders to manufacture nano/micro drug delivery systems e.g manufacturing of nano/micro particles (or capsules). The methods used currently for preparing nano/micro particles are mainly based on double emulsion methods or solvent exchange technique.

The major problems with the current methods are the low drug loading capacity, low loading efficiency, and poor ability to control the size distribution. Utilization of nanotechnologies, such as nanopatterning, could allow manufacturing of nano/micro particles with high loading efficiency and highly homogeneous particle sizes. Nanotechnology has a potential to increase in efficacy of existing drug delivery systems by orders of magnitude. As an example nano/micro devices can be developed for both diagnosis and therapy (theragnosis) using the same device, and such theragnosis devices hold great promises in personalized medicine. Futuristic nanotechnologist do expect patients to drink fluids containing nanorobots programmed to attack and reconstruct the molecular structure of cancer cells and viruses in the future. There's even speculation that nanorobots could slow or reverse the aging process, and life expectancy could increase significantly. Nanorobots can also be programmed to perform delicate surgeries. These nanosurgeons could work at a level a thousand times more precise than the sharpest scalpel. By working on such a small scale, a nanorobot could operate without leaving the scars that conventional surgery does. Moreover, nanorobots could change the physical appearance of a person. They could be programmed to perform cosmetic surgery, rearranging atoms to change ears, nose, eye colour or any other physical feature one wishes to alter. Many nanotechnologist think that these applications are well outside the scope of possibility, at least for the near future. They warn that the more fascinating applications are only theoretical. Some are anxious that nanotechnology will end up like virtual reality -- in other words, the hype surrounding nanotechnology will continue to build until the limitations of the field becomes a public knowledge, and then interest and funding will quickly disperse. However considering the rewards that have been gained what is being said “there is plenty of room at bottom” remains factual.

Medha Joshi is faculty Department of Pharmaceutics, Utrecht University, The Netherlands and Vandana Patravale is faculty Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai

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