Nanomedicines and infectious disease

Understanding chemistry at nano-scale level is considered to be fascinating and often very rewarding. Nanotechnology was vastly experimented against life threatening diseases since ages. However, revolution in nanotechnology was initiated in the year 1959 at CalTech (USA) by the famous lecture of Richard Feynman¹. Thereafter, lots of blockbuster nanomedicines came into market and received FDA status such as ‘AmBisome’ (liposomal Amphrotericin B), ‘Abraxane’ (serum albumin entrapped paclitaxel), ‘Doxil’ (liposome bound anticancer), ‘Cimzia’ (antibody protein attached to polymer), ‘Pegasys’ (PEGylated IFN alpha-2a protein), ‘Adynovate’ (Polymer-protein conjugate), etc.

Nanomedicines therapy exhibits unique benefit due to high solubility, thermo-sensitivity, controlled releasing capacity, easy surface modulation and high surface area to volume ratios. These exceptional features allow to get rid of increased drug resistance problem of anti-infectious agents. In addition, nanomedicines are able to deliver drugs across the tight impermeable blood brain barrier (BBB) that protects the inner blood circulation of the brain from rest. Thus, viruses like HIV/AIDS or TB that forms a reservoir in brain can be treated by nanomedicines efficiently². There are different forms of nano-based drug delivery systems including nanocapsules, liposomes, dendrimers, nano-biomagnetic, attapulgite clays with nano-pores, nanovaccines, quantum dots, nanotubes and nanogels studied against various infectious diseases. Nanomedicines are also useful as an adjuvant therapy to enhance the immune stimulatory properties of traditional vaccines. ‘MF59’ is a nanosized oil-in-water emulsion (<250 nm) developed from squalene which is used as an adjuvant for influenza vaccine in many countries and is the only vaccine adjuvant approved by the FDA. Nanoemulsions also successfully used to deliver Hepatitis B antigens for needle free nasal immunization. Solid lipid nanoparticles loaded with rifampicin, isoniazid, and pyrazinamide shows higher recovery from tuberculosis after single administration compare to pure drugs³. Liposomes nanocarriers encapsulated with indinavir showed efficient delivery of the drug to lymphoid tissues and successfully reduced HIV viral load⁴. Metallic nanoparticles such as Ag, Au, Cu, Ti, Fe or metal oxides have shown significant antimicrobial, antifungal, and antiviral activities. It is proved that metal nanoparticles and metal ions produces free radicals that lead to oxidative stress through reactive oxygen species generation which ultimately induce damage in microbial proteins and DNAs and lead to death⁵. Some nanoparticles shows inherent antimicrobial activities called as nano-antibiotics. For example, nitric oxide-releasing nanoparticles have been shown to inhibit the growth of antibiotic-resistant strains of P. aeruginosa, E. faecalis, K. pneumoniae, and E. coli. Their antimicrobial activity mostly depends upon generation of reactive nitrogen oxide intermediates (RNOS), bacterial DNA damage, subsequent deamination of nucleotides, etc⁶. This multiple killing mechanisms of nano-antibiotics make them more advantageous over other conventional antibiotics.

Therefore, Nanomedicines are compelling new generation tools to combat many infectious diseases.

 References

1. R.P. Feynman, There’s plenty of room at the bottom, Eng Sci, 1960, 20, 17.
2. H.Y. Dou, C.B. Grotepas, J.M. McMillan, C.J. Destache, M. Chaubal, J. Werling, J. Kipp, B. Rabinow and H.E. Gendelman, Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS, J. Immunol.,2009, 183, 661.
3. R. Pandey, S. Sharma and G.K. Khuller, Oral solid lipid nanoparticle-based antitubercular chemotherapy, Tuberculosis (Edinb), 2005, 85,415.
4. L. Kinman, S.J. Brodie, C.C. Tsai, T. Bui, K. Larsen, A. Schmidt, D. Anderson, W.R. Morton, S.L. Hu and R.J. Ho, Lipid-drug association enhanced HIV-1 protease inhibitor indinavir localization in lymphoid tissues and viral load reduction: a proof of concept study in HIV-2287-infected macaques, J. Acquir Immune Defic Syndr., 2003, 34, 387.
5. R.P. Allaker and G. Ren, Potential impact of nanotechnology on the control of infectious diseases, Trans R Soc. Trop Med. Hyg., 2008, 102, 1.
6. R.Y Pelgrift and A.J. Friedman, Nanotechnology as a therapeutic tool to combat microbial resistance, Adv. Drug Deliv. Rev., 2013, 65, 1803.