Strategies for controlling the pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, biorecognition, and efficacy of drugs have led to the development of Novel Drug Delivery Systems (NDDS). NDDS strategies are based on interdisciplinary approaches that combine polymer science, pharmaceutics, bio-conjugate chemistry, and molecular biology. To minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required site, various drug delivery and drug targeting systems are currently under development.
The choice of a drug delivery routes is driven by patient acceptability, the properties of the drug (such as its solubility), access to a disease location, or effectiveness in dealing with the specific disease. The most important drug delivery route is the peroral drug delivery. An increasing number of drugs are protein and peptide-based. At present, protein drugs are usually administered by injection, but despite the barriers to successful drug delivery that exist in the gastrointestinal tract (i.e., acid-induced hydrolysis in the stomach, enzymatic degradation throughout the gastrointestinal tract by several proteolytic enzymes, bacterial fermentation in the colon), the peroral route is still the most intensively investigated as it offers advantages of convenience and cheapness of administration, and potential manufacturing cost savings.
Inhalation drug delivery is second important and is effected in a variety of ways - via aerosols, metered dose inhaler systems (MDIs), powders (dry powder inhalers, DPIs) and solutions (nebulizers), all of which may contain nanostructures such as liposomes, micelles, nanoparticles and dendrimers. Aerosol products for pulmonary delivery comprise more than 30% of the global drug delivery market. Research into lung delivery is driven by the potential for successful protein and peptide drug delivery, and by the promise of an effective delivery mechanism for gene therapy (for example, in the treatment of cystic fibrosis), as well as the need to replace chlorofluorocarbon propellants in MDIs. Pulmonary drug delivery offers both local targeting for the treatment of respiratory diseases and increasingly appears to be a viable option for the delivery of drugs systemically.
Transdermal drug delivery avoids problems such as gastrointestinal irritation, metabolism, variations in delivery rates and interference due to the presence of food. It is also suitable for unconscious patients. The technique is generally non-invasive and aesthetically acceptable, and can be used to provide local delivery over several days. Parenteral drug delivery routes (intravenous, intramuscular, subcutaneous) are very important. The only nanosystems presently in the market (liposomes) are administered intravenously. Nanoscale drug carriers have a great potential for improving the delivery of drugs through nasal and sublingual routes, both of which avoid first-pass metabolism; and for difficult-access ocular, brain and intra-articular cavities. For example, it has been possible to deliver peptides and vaccines systemically, using the nasal route, thanks to the association of the active drug macromolecules with nanoparticles. In addition, there is the possibility of improving the occular bioavailability of drugs if administered in a colloidal drug carrier.
The global pharmaceutical market is in phase of continuous dynamic transition and growth. The world pharma market has grown from US$ 337 billion in 1999 to US$ 406 billion in 2002 to a current of about US$ 600 billion.
Trans-tissue and local drug delivery systems require to be tightly fixed to resected tissues during surgery. The aim is to produce an elevated pharmacological effect, while minimizing systemic, administration-associated toxicity. Trans-tissue systems include: drug-loaded gelatinous gels, which are formed in-situ and adhere to resected tissues, releasing drugs, proteins or gene-encoding adenoviruses; antibody-fixed gelatinous gels (cytokine barrier) that form a barrier, which, on a target tissue could prevent the permeation of cytokines into that tissue; cell-based drug delivery, which involves a gene-transduced oral mucosal epithelial cell (OMEC)-implanted sheet; device-directed delivery - a rechargeable drug infusion device that can be attached to the resected site.
Gene delivery is a challenging task in the treatment of genetic disorders. In the case of gene delivery, the plasmid DNA has to be introduced into the target cells, which should get transcribed and the genetic information should ultimately be translated into the corresponding protein. To achieve this goal, a number of hurdles are to be overcome by the gene delivery system. Transfection is affected by: (a) targeting the delivery system to the target cell, (b) transport through the cell membrane, (c) uptake and degradation in the endolysosomes and (d) intracellular trafficking of plasmid DNA to the nucleus.
Global perspective
The global pharmaceutical market is in phase of continuous dynamic transition and growth. The world pharma market has grown from US $ 337 billion in 1999 to US $ 406 billion in 2002 to a current of about US $ 600 billion. In the global pharmaceutical market novel drug delivery systems make up about 15% of the total market share, which means US $ 75 billion.6 The top pharma players worldwide spend about 14-15 percent of their sales in research and development. Globally the revolutionary discoveries in the field of genomics, proteomics and biotechnology require innovative drug delivery systems for optimum benefits to the patients.
Indian scene
Indian pharma industry, 4th largest by volume and 13th largest by value has shown a remarkable presence in global frontiers, with market size expected to reach to about US $ 25 billion by 2010.With 40 percent of the US drug master filings (a regulatory requirement for bulk drugs), 20% of the total ANDA filings, the presence of our pharmaceutical industries in generic market is significant. During the past decade, the R&D in India has targeted generic market. But now the existing market is under threat from the patent term extensions and authorized generics practiced by the innovators, the national pharma industries are facing challenge due to the generic market saturation.Hence, the Indian pharmaceutical fraternity has to gear up to overcome the challenges by focusing on other research area to sustain growth and quantum in pharmaceutical market. Out of the domestic pharmaceutical market, 80% is contributed by formulations and merely 5% is occupied by NDDS. It is suggestible of enormous growth potential of NDDS in minimum time and at affordable cost.
The challenges of dynamic epidemio-logical and health transition, increased expectancy of life, shift The future of the drug delivery is to be the era of nanomedicine. Nanomedicine beholds promises like biological mimetics (nanotubes), technologies like molecular self assembly (e.g. nanofibres of peptides for tissue engineering, shape-memory polymers as molecular switches, nanoporous membranes), nanoscale implantable devices/silicon microchips ornanochips for nanoparticle release, or multi reservoir drug delivery-chips, micro-machined hollow needles and two-dimensional needle arrays from single-crystal silicon), paramagnetic nanoparticles for targeted drug delivery in the disease pattern from acute infectious diseases to chronic disease, increasing instances of cancer and genetic diseases and enforcement of product patent regime from Jan 2005 have triggered the research focus towards NDDS.The driving force to capitalize on the opportunity in NDDS in India lies in how swiftly technical skills of available manpower is utilized to achieve the goals of NDDS research. Availability of technically skilled manpower is not only sound in knowledge but also cost effective and can be effectively utilized to realize cherished goals.
Being less time consuming and less costly option to climb the ladder,major Indian companies, such as Ranbaxy, Dr Reddy's Laboratories, Nicholas Piramal, Cipla, Lupin ,Wockhardt, Sun Pharmaceutical Industries, Cadila Healthcare, Cipla, Pancea Biotec and Nicholas Piramal etc. , have startedfocusing on Novel Drug Delivery Systems (NDDS). Emerging attraction towards this highly specialized arena of life science is provided by government with initiatives like tax and duty exemptions for R & D companies, rapid regulatory clearances, setup of educational centers of excellence in the pioneering NDDS, providing grants and financial aids for institutions involved in the area of NDDS and nano-biotechnology, reduction in the number of the drugs under the price control.India with its excellent innovative and scientific capabilities has emerged as the hub for the global research and attracted many multinational giants for their R & D centers in India. With the identified necessity and the enormous potential for growth the Indian pharma industries have to the shift from the conventional paradigm of business based research to research based business in this unique field NDDS.
Future
We have to set up a vision for the new India dreams. Indian companies will undoubtedly get into exciting challenge of new drug delivery research, both to meet Nation's needs as well as to explore the great potential in the global market. A fundamental understanding of the disease at the genetic, molecular and cellular level will open new vistas for curative, preventive and predictive medicines. The future of the drug delivery is to be the era of nanomedicine. Nanomedicine beholds promises like biological mimetics (nanotubes), technologies like molecular self assembly (e.g. nanofibres of peptides for tissue engineering, shape-memory polymers as molecular switches, nanoporous membranes), nanoscale implantable devices/silicon microchips ornanochips for nanoparticle release, or multi reservoir drug delivery-chips, micro-machined hollow needles and two-dimensional needle arrays from single-crystal silicon), paramagnetic nanoparticles for targeted drug delivery.
The application of nanotechnology like that in diagnostic purpose, drug delivery, gene delivery, biological imaging, tissue engineering, selective cell targeting are a declaration of war on cancer and chronic genetic diseases such as diabetes, cardiovascular diseases, neurodegenerative disorders, obesity, aging etc... We have to create successful networks in the form of an Indian Research Consortium incorporating industries, government labs, and universities to best use the available resources and avoid waste and duplication of research work to achieve our cherished goals in minimum time and cost.
(The author is professor and head, Pharmacy Department, & Coordinator, TIFAC-CORE in NDDS, Pharmacy Department,Faculty of Tech.and Engg., The Maharaja Sayajirao University of Baroda, Vadodara)