Background of nanomedicine
Nanotechnology is a multidisciplinary field covering the design, manipulation, characterisation, production and application of structures, devices and systems at nanometer sacle (1 : 500nm size range). At this size range they present unique or superior physicochemical properties. This scale represents that of atoms, molecules and macromolecules. The application of nanotechnology in the heath care sector, inimgaging, diagnostics, drug delivery and therapeutics, also referred to as nanomedicine, has gained ground over the past 5 years. This can be observed from the increase in the USA budget for nanomedicine research, as well as an increase in the number of nano-pharmaceutical patents. Nanomedicine has been applied since the 1960’s, with the first lipid vesicles known as liposomes. The current growth in this field is mainly due to the advances in nano science in better approaches of molecular assembly and the design of more controlled and efficient nanomaterial. The field of drug development experience very low success rates with regards to drugs that enter market. These shortfalls are due to factors such as toxicity of the therapeutic compounds, non specificity, poor solubility leading to lowered bioavailabity and thus reduced efficacy.
Size as the main factor improves properties – Size Matters
The sub-micron size of nanoparticles offers a number of distinct advantages over microparticles particularly in drug delivery due to the fact that these particles are in the size region of macromolecules. The physical characteristics, particularly for particles less tahn 100 nm in size allows these particles to reach virtually all tissues in the body. Nanoparticles have in general, relatively higher intracellular uptake compared to microparticles. This was demonstatrated by Desai et al. (1997), whereby 100 nm size nanoparticles showed a 2.5 fold greater up-take compared to 1 um and 6 fold higher up take compared to 10 um microparticles in caco-2 cell line. This aspect of intracellular uptake is more critical for intracellular pathogens such as infectious diseases, where the drug needs to act intracellularly. Thus by nanoencapsulating the product, one can attain intracellular delivery. Furthermore these particles can cross barriers that in general make it difficult for conventional therapeutic compounds to reach the target.
Reports on nano-particles crossing the blood brain barrier (BBB), the stomach epithelial and even the skin have been presented. When orally taken, free therapeutic agents are absorbed into the systematic circulation via the portal blood and undergo first pass metabolism, leading to poor bioavailability of drugs. However, when in a Nan format, transport of these products will, in addition to entry via the portal blood, be through the Peuer’s patches, followed by uptake via the M cells, entry into the intestinal lymphatic transport and thus into systemic circulation. This mode of transport, which includes, endocytosis and phagocytosis will thus minimise the first pass hepatic metabolism of the therapeutic agents, therefore improving their bioavailability.
The nanocarriers can also be optimised to nanoencapsulate both hydrophilic and hydrophobic therapeutic compounds. In addition, nano sized particles have very high surface area per unit volume, and this has revolutionised the field of delivery through improved bioavailability of most therapeutic compounds that generally have poor bioavailability.