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First Workshop on Nanomedicine for Infectious Diseases of Poverty, 2731 March 2011, Magaliesberg, South Africa

May/June 2011

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Table of Contents


Introduction

An international workshop on nanomedicine for infectious diseases related to poverty was held in Magaliesberg, South Africa from 27–31 March 2011. The meeting was organised by Dr Hulda Swai, chair of the nanotechnology programme at the Council for Scientific and Industrial Research (CISR), a multidisciplinary science and research institute established in 1945 and funded by the South Africa Department of Science and Technology and Economic Commission for Africa (ECA). CSIR is one of two SA government-funded centres with nanomedicine programmes (the other is MINTEC). About 70 delegates from 20 countries attended the workshop.

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Nanotechnology is being used in many different aspects of medical care including therapeutics, new drug delivery systems, diagnostics, imaging and surgical procedures. This article principally focuses on new formulations of drugs and drug delivery systems. Nanomedicine -- the application of nanotechnology to medicine -- has a relevance for HIV and related infections that rarely gets much attention.

Most of the focus on pipeline drugs for HIV and TB is on new compounds or new oral formulations of already approved drugs. However, for the last fifteen years various laboratories have been working with nanoformulations of antriretrovirals, though none have yet resulted in new medicines.


Size and Scale

The simplest explanation of nanomedicine is based on a size ranging from 10-100 nm, though the EU definition has an upper range of 1000 nm. One nanometer is one-billionth of a meter (the width of about five atoms). See Table 1.

At this scale particles have different physical properties relating to surface to volume ratio, surface tension, surface charge and quantum dot effect and this can enhance drug bioavailability and solubility. Engineering molecules to target specific cellular and tissue targets has the potential to overcome barriers to sanctuary sites including the blood-brain barrier. Although nanotechnology is generally associated with the concept of the smaller particles, nanomedicine is actually based on drug formulations that are larger that pure drug molecules.

Figure 1: Comparative Sizes of Nanoformulation Particles

Factor of 10 Metric Size Example Size Comment
10 (0) 1 m (1000 mm) a child
10 (-1) 100 mm an orange
10 (-2) 10 mm a marble
10 (-3) 1 mm (1000 um) a pin head (1mm)
grain of salt and an amobea (both ~500 um)
10 (-4) 100 um human egg (130 um)
hair width (100 um)
10 (-5) 10 um Red blood cell (8 um)
Chromosome (7 um)
baker's yeast (3 x 4 um)
mitochondrion (4 x 0.8 um)
E. coli bacterium (3 x 0.6 um)
cells
10 (-6) 1 um (1000 nm) measles virus (220 nm)
HIV (130 nm)
influenza (130 um)
phage (bacteria virus) (70 x 200 um)
viruses, bacteria
10 (-7) 100 nm hepatitis virus (45 nm)
rhinovirus (30 nm)
ribosome (30 nm)
viruses, bacteria
10 (-8) 10 nm antibody (12 nm)

tRNA (7 nm)

haemoglobin (6.5 nm)

molecules
10 (-9) 1 nm (1000 pm) adenine (1300 x 760 pm)
methionine (1100 x 700 pm)
glucose (900 pm)
carbon atom (340 pm)
water molecule (275 pm)
molecules
10 (-10) 100 pm hydrogen atom (100 pm) atoms
10 (-15) nucleus

Note: relative size from 10 (0) to 10 (-10) is similar to comparing the size of the world to a golf-ball.

Attaching compounds to larger molecules or encapsulating them inside other molecules can deliver a drug to the target site more accurately. This can overcome one of the main limitations of current oral formulations, where over 90% of medicines are excreted unused.

These improvements include:

  • Better bioavailability, as an example this could be achieved by designing formulations that overcome hydrophobic or hydrophilic properties of individual molecules.
  • Reducing drug wastage by overcoming protein binding and during oral absorption, where >90% of the active compound of antiretroviral drugs are cleared by blood filtration through the liver or kidneys before it is able to act on HIV.
  • More targeted delivery should reduce the quantity of raw materials needed. This, is turn, has the potential to have the biggest impact on drugs used in resource-limited settings. Even though the drugs are much cheaper in poorer countries a much higher percentage of the costs is related to the active pharmaceutical ingredients (API).
  • Reducing toxicities related to the metabolism of current oral formulations. For example, if a nanoformulation is designed to increase active drug levels inside cells while keeping blood levels low this has the potential to reduce toxicities related to systemic drug levels.
  • Sanctuary site penetration by developing formulations that target immune cells that can cross the blood-brain barrier. In a similar way molecules may be designed to use cells to evade drug transporters such as P-gp that limit penetration of other sites.

However, while the potential benefits are promising, they also bring significant challenges to safety and regulatory approval.

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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
 
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