Nanotechnology/nanoscience is revolutionising drug delivery. The aim ofresearch within this field is to prevent, control, and treat infections and/or diseases by delivering drugs more effectively, making sure they are ‘targeted’ – delivered to exactly where they are needed in the body. This has already led to dramatic improvements in the treatment of a number of conditions.
Nanoparticles have shown impressive impact in treating various cancers such as ovarian, skin and breast. Doxorubicin was the first nanoparticle used in cancer chemotherapy; the drug was encapsulated in anionic liposomes which showed accumulation in tumours. There are currently two liposomal formulations of doxorubicin: Doxil, an FDA-approved polyethylene glycol (PEG) coated liposomeused to treat AIDS-related cancers, and Myocet, a non-peglated version with fewer side effects than Doxil which is approved in Europe to treat breast cancer. There has been increasing interest in delivering oligonucleotides using nanoparticles. One recent study showed multiple strands of antisense DNA attached to gold nanoparticles were much more effective than the antisense DNA alone, they provided improved stability, reduced degradation and were readily absorbed by cells.
Antibiotics revolutionised the treatment of infectious diseases when they were first discovered in the 1940s. However, over the intervening decades, continued use of antibiotics to treat a wide range of conditions has led to increased levels of antibiotic resistance. We are now moving into a “post-antibiotic era”, where once treatable infections no longer respond to antibiotics. This issue is already limiting the types of medical interventions that are possible and it will continue to do so, increasingly, until there are effective alternatives.
One alternative to antibiotics is the use of biocides to treat infectious diseases. The basic hypothesis tested is: if antibiotic resistance is the problem, then we need to find a way of delivering antimicrobials that does not give rise to resistance. Biocides are less prone to the development of resistance than antibiotics because they attack multiple celluar targets. If nanotechnology platforms could be used to deliver biocides to infected body sites, they could kill the infecting microbes and resolve the infection.
There are a few polymers that can be used as delivery systems that are already FDA approved. Poly lactic-co-glycolic acid (PLGA) is commonly used because it is hydrolysed to its monomers: lactic acid and glycolic acid, and these are readily metabolised in the body via the Krebs cycle. Hydrophobicity of the hydrophobic PLGA polymer can be increased to aid solubility and membrane transfer by the addition of polyethylene glycol (PEG). Specific target delivery can be achieved through surface modification by attaching a receptor or ligand to the surface of PEG.
Initial laboratory testing has demonstrated that polymer microparticles loaded with oxidative biocide precursors can be used to deliver a target dose of the biocides hydrogen peroxide and peracetic acid. These biocides exhibited rapid and sustained killing of several antibiotic-resistant bacteria, including methicillin-resistant Stahphylococcus aureus (MRSA) and carbapenem-resistant E. coli. A cytotoxicity assay demonstrated that the loaded microparticles had a low level of toxicity, so are likely to be well-tolerated. The next stage of the research is to apply this technology to the treatment model infection and human infection. This will require further investment to fund clinical trials.