Back in 1959, R. P. Feynman, a physicist, advocated the need for scaling down to 'nano' level and starting from the bottom as key ingredients to future technology and advancement, in his talk on 'nanoscale'. Feynman said, "There's plenty of room at the bottom. But there's not that much room to put every atom in its place, a vision articulated by some nanotechnologists would require magic fingers." Nearly five decades after his speech, the world is indeed experiencing the big effects and is still awaiting the untapped huge potential of this small science. Such multifaceted are its applications that it has not deterred from revolutionizing the medical research, which is moving ahead by leaps and bounds.
Indeed, nanotechnology has the potential to produce low-cost, self-replicating systems that could revolutionize the scientific landscape. The emergence of nanotechnology is likely to have a significant impact on drug formulation sector, affecting every route of administration from oral to injectable. Also, the payoff for doctors and patients should be lower drug toxicity by encapsulating the drugs, which trigger the immune response and offer other harmful side effects, reduced cost of treatments, improved bioavailability, controlled dosage release into the human body and an extension of the economic life of proprietary drugs for the manufacturers.
The emergence of high-throughput screening has led to an increase in the number of poorly water-soluble drugs. The delivery of such drugs into the body in a sufficiently bioavailable form have been a challenge for formulation researchers, especially if the drug was insoluble in an organic medium. Although several approaches, such as solubilization, cosolvency, complexation with beta-cyclodextrin and solid dispersion can enhance a drug's dissolution, these methods are limited and suffer from disadvantages, including environmental concerns (e.g., because of the need for organic solvents), low drug loading and large doses.
In the recent years, nano-scale drug delivery technology is being exploited to tackle such formulation problems associated with poorly water-soluble and lipid-soluble drugs. Nanocarriers, ranging in size from 1 to 1000 nm, are being used as drug delivery agents. The reduction of drug particles to the nano-scale increases dissolution velocity and saturation solubility, which leads to improved in vivo drug performance.
Nanocarriers for drug formulations could be produced by either dispersion-based processes (which involve breaking larger micrometer-sized particles into nanoparticles) or precipitation-based processes (which involve nucleation of particles from the molecular state). The production processes should necessarily exhibit features such as:
■ Be simple, continuous and efficient
■ Be viable for large-scale production
■ Effectively screen out most microsized particles
■ Be acceptable to regulatory authorities
Various processes such as wet milling, high-pressure homogenization, emulsification, precipitation, rapid expansion and spray freezing can be used to produce nano-scale drug formulations.
As per reports, industry bags about $65 billion of its revenue from pharmaceuticals with poor bio-availability, which far too often results in higher patient costs and inefficient treatment and more importantly, increased risks of toxicity or even death. Because nano-scale drug delivery technology focuses on 'the very small', it is uniquely suited to create systems that can better deliver drugs to tiny areas within the body. Nano-scale drug formulation also makes it possible for drugs to permeate through cell walls, which is of critical importance to the expected growth of genetic medicine over the next few years. Various such nanotechnologies have also been commercialized.
Considering the applications of nanotechnology in drug formulation, the next ten years will see nanotechnology based drug delivery playing the most dominant role in the global business environment and is expected to cross the figure of $180 billion.
The huge potential of this technology has prompted the government of India to support various research and commercialization activities to avail these nanomedicines to the domestic market. India is exploiting this field in order to meet its most pressing need of making the benefit of science available to the poor. These nanotechnology initiatives are expected to strengthen the country's economic growth. India is expected to occupy a promising position in health related nanotechnology patent activity, holding a 0.5 per cent of the global patents share in a recent survey conducted by AZojono, an online journal for nanotechnology.
The Department of Science and Technology through its Nano Science and Technology Initiative (NSTI) supports R&D by individual scientists. It has been instrumental in the establishment of research facilities and setting up core groups and awareness programs through seminars and conferences. These efforts have been reinforced by the Department of Biotechnology, which has been funding many projects on nanobiotechnology. The department of industrial policy and promotion under the Ministry of Commerce and Industry has also prepared a program on applications of nanotechnology in the manufacturing sector to be submitted to the planning commission for the 10th plan.
Research in nanotechnology based drug delivery is being carried out in about 20 academic and scientific institutions, including UICT (Mumbai), University of Delhi, IIT (Mumbai, Kharagpur, Delhi), IISc (Bangalore), NCL (Pune), NIPER (Chandigarh) and CCMB (Hyderabad). NIPER, the Indian National Institute of Pharmaceutical Education and Research, is planning to take up the ambitious task of developing regulatory guidelines for approving nanotechnology-based drugs. The attempt would be to come out with standard parameters to test nanotoxicity of the nanoparticulate drug delivery systems. The move turns significant in the wake of increasing R&D by Indian companies to develop nanodrugs.
Nanotechnology based drug formulations have not just been limited to the academic research laboratories but have also set to revolutionize the Indian pharmaceutical market. Velbionanotech, ranked as Asia's top 100 bio-nanotechnology companies by Red Herring in 2005, is designing drugs for various diseases such as heart disease, kidney stones, AIDS, cancer and cosmetic generic products, using short fragments of DNA as a new type of a drug. These drugs assembled in nanochips and as nanoparticles to be delivered in the human body, are effective in curing the sick/diseased and healing the injured. Velbionanotech products and technology deal with alleviating the disease at the molecular level. Apart, `nanoxel', a novel formulation for the widely used anti-cancer drug paclitaxel, has recently been launched by Dabur Pharma Ltd, as India's first indigenously developed nanotechnology based chemotherapy agent. The product is also expected to reach the European market as well as other countries after the initial clinical trials soon to be conducted.
Companies like Hyderabad-based Dr. Reddy's Research Laboratory, Ahmedabad-based Cadila pharma, Bangalore-based Biocon India Ltd Hyderabad-based Shantha Biotech are actively involved in the development of various nano-carriers for the delivery of therapeutic proteins and immunomodulators. Yet another company involved in the area of nanomedicine research is the New Delhi-based Panacea Biotech Ltd. The company's biopharmaceutical research centre is proposed to utilize modern tools such as genetic engineering, molecular biology, cell biology and genomics knowledge base to develop novel preventive and therapeutic nanoparticulate drug delivery systems, vaccines, bioactive therapeutics and monoclonal antibodies for therapeutic use. Some other achievements in the area of nanotechnology based drug formulations include development of an improved ophthalmic formulation using smart hydrogel nanoparticles and oral insulin formulation using nanoparticles/ carriers.
With all these efforts, the day is not far for India to emerge as a world leader in the area of nanotechnology. Nanotechnology in drug formulations can prove to be a great boon to the Indian society. Numerous grave diseases, which loom over the country, like tuberculosis, malaria, AIDS and cancer could be efficiently tackled by the apt application of this technology in developing efficacious drug formulations. These formulations could have the potential to overcome the 'deficient' present day treatment.
Multiple applications of nanotechnology in drug formulations have been patented and published by research groups of UICT. Our research group at UICT has made rapid strides in developing various nanocarriers, including NanOsorbs, nanojects, nanogels, NanOjelly and SMETs, based on different approaches including polymeric/solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and liquid crystalline nanocarriers. A nanostructured lipid carrier based oral and I.V. formulations for the treatment of malaria have been developed and tested in murine models. The toxicity studies are completed. These products are expected to enter the clinical trials very soon.
Though India is heading towards completely novel, nanotechnology platform based drug formulations, there are some challenges, which need to be conquered. Toxicity issue of the nanoparticulate drug delivery systems needs to be carefully studied. Weighing the economical aspects of these formulations against the host of benefits offered is yet another area, which has to be looked into. Also, it is importance to create awareness amongst the medical practitioners regarding these systems since they form a vital link between the manufacturers and the Indian society. Fundamental research is thus required for tackling these issues and for successful application of nanotechnology in medicine. Rationale design of nanotechnology based drug delivery systems and devices based on the proper understanding of the biological processes associated with diseases will be instrumental in day-to-day implementation of nano-scale drug formulations.
(The authors are from Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai)