Indian Journal of Experimental Biology Vol. 44, May 2006, pp. 357-366 Review Article Nanotechnology based drug delivery system(s) for the management of tuberculosis Rajesh Pandey & G K Khuller* Department of Biochemistry, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India The era of nanotechnology has allowed new research strategies to flourish in the field of drug delivery. Nanoparticle- based drug delivery systems are suitable for targeting chronic intracellular infections such as tuberculosis. Polymeric nanoparticles employing poly lactide-co-glycolide have shown promise as far as intermittent chemotherapy in experimental tuberculosis is concerned. It has distinct advantages over the more traditional drug carriers, i.e. liposomes and microparticles. Although the experience with natural carriers, e.g. solid lipid nanoparticles and alginate nanoparticles is in its infancy, future research may rely heavily on these carrier systems. Given the options for oral as well as parenteral therapy, the very nature of the disease and its complex treatment urges one to emphasize on the oral route for controlled drug delivery. Pending the discovery of more potent antitubercular drugs, nanotechnology-based intermittent chemotherapy provides a novel and sound platform for an onslaught against tuberculosis. Keywords: Alginate, Liposomes Nanoparticles, Poly lactide-co-glycolide, Tuberculosis. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is a major infectious burden worldwide and statistical estimates continue to worsen with each passing year (Table 1) 1-5 . The control of TB oscillates around a preventive arm, i.e. vaccination and a therapeutic arm, i.e. chemotherapy. Vaccination is the most desirable means of preventing TB. The reason behind the success of vaccines, in general, lies to a large extent in their ability to enable the body to respond to the invading microbes, rather than directly treating the disease with antibiotics. However, the currently available vaccine for TB, i.e. Bacillus Calmette Guerin (BCG) suffers from several demerits such as a variable efficacy in different populations, limited success against pulmonary TB that accounts for most of the disease burden and short-term immunity 6 . The current trend is the development of subunit vaccines by using molecular techniques for the isolation of different macromolecules of disease causing organisms. Nevertheless, it is realized that several years, if not decades, would elapse before a candidate TB vaccine could take over BCG and is precisely the reason why an improvement in the current TB-chemotherapy should be the immediate short-term goal. It has been a long time since an effective chemotherapeutic regimen is available for TB; however, the treatment schedule poses several problems that can result in therapeutic failure. Among these problems, the foremost is the need to administer multiple antitubercular drugs (ATDs) daily that is frequently associated with patient non-compliance. Further, most of the frontline ATDs are hepatotoxic and at least in some patients they fail to eradicate persistent bacilli 4 . The ongoing DOTS (Directly Observed Treatment, Short course) programme has not been completely successful in solving the problem of patient non-compliance 3 . Most of the patients fail or are unable to adhere to multidrug therapy daily for such a longer period. Even the principal cause for the generation of drug resistant TB generally appears to be associated with low patient compliance. The __________ *Correspondent author Phone: 0172-2755175 Fax: 0172-2744 401, 2745 078. E-mail: gkkhuller@yahoo.co.in Table 1 — Salient statistical estimates for tuberculosis 1-5 • Affects one-third of the world’s population, i.e. nearly 2 billion individuals • Responsible for 3 million deaths annually • Most of the infections are latent with a 2-23% lifetime risk of developing reactivation TB • India accounts for 20% of all new TB cases in the world each year • Resistance to key frontline anti-TB drugs range from 1-10% • The United Nations Millennium Development Goals (MDGs) for a 50% reduction in TB prevalence and deaths globally between 1990 and 2015 is a formidable task especially in endemic zones