Biodegradable Nanostructures – A Novel Means of Combating Antibiotic Resistance

May 10th, 2011
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Antibiotic resistance: Two words that strike fear in physicians, hospital workers, and patients and which increasingly grab the attention of media outlets throughout the world.
Nanotechnology, the branch of engineering that deals with things smaller than 100 nanometers (especially with the manipulation of individual molecules), continues to make inroads in various areas of medicine and life sciences. Over the past several years we have seen advances in nanomaterials that provide the basis for diagnostic tests, improved vehicles for drug delivery, and novel therapeutics. Among those advances, applications related to the development of novel drugs are especially interesting, particularly where hope in the fight against highly drug-resistant bacteria may be offered.  The ability to carefully engineer nanomaterials to specifically interact with biomolecules suggests that further developments in the therapeutic use of nanomaterials are likely to emerge. Engineered nanomaterials that have ideal drug properties – namely, high selectivity (an ability to hit very specific molecular targets), well understood mechanisms of action that provide high efficacy, and limited side effects – are now on the horizon. So the potential for nanomaterials to replace existing biologics, including monoclonal antibodies and recombinant proteins, is a possibility.

Researchers at the IBM labs in San Jose have recently made an interesting contribution to the field. They sought to address the widespread problem of antibiotic resistance in bacteria and have developed biodegradable nanostructures that cause selective lysis (breakdown) of bacterial membranes. Their approach provides a novel twist on some older technology that has shown promise, but has stalled owing to a lack of selectivity.  The IBM team recognized the potential of a series of known peptides with potent antibacterial activity. These peptides, which include magainins, alamethicin, protegrins, and defensins, have been known to have potential as antibacterial agents for some time. They typically form amphipathic (charged) helices that can punch holes in bacterial membranes, thus causing those bugs to spill their guts in a manner that leaves little or no opportunity to acquire resistance.  But such peptides indiscriminately poke holes in blood cells as well as bacteria due to their lack of selectivity.
The IBM team overcame this problem via the development of cationic amphiphilic polycarbonate structures that self-assemble into micelles, or tiny spheres, when exposed to water.  These molecules turn out to be more highly selective for bacterial membranes than for blood cells, thus breathing new life into the potential for this approach to tackle bacterial infections. The investigators went on to show that their molecules are biocompatible, biodegradable, have low toxicity, and that they have tunable mechanical properties – all good qualities for a new class of antibiotics. In short, the polycarbonate polymers mimic the activity of earlier antibacterial peptides but they now have the ability to selectively hit bacteria rather than blood cells. The IBM nanostructures are effective against several types of gram positive bacteria, including E. faecalis, S. aureus, and MRSA (methicillin resistant S. aureus).  Interestingly the compounds are also active against the fungus C. neoformans.
So we are starting to see elements of molecular design and higher binding selectivity introduced into the world of nanomaterials. We are not yet at a point where we can design levels of binding selectivity that are comparable to antibody binding, but we are now a few steps along that path. Do you agree that this will ultimately lead to the creation of better drugs and diagnostic products? What other uses for this scientific breakthrough do you envision? Please share your thoughts here.

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About the Author:

I have more than 20 years of R&D and business development experience in the life sciences and pharmaceutical industry. I’ve led research teams involved in all aspects of drug discovery and have designed, negotiated and managed many R&D collaborations. I also have extensive experience in technology evaluation, technology development, and strategic planning. Send me an email.