Feature: Small is big in drug delivery

This feature appeared in the July/August 2011 issue of Australian Life Scientist. To subscribe to the magazine, go here.

While the last couple of decades has witnessed many advances in the development of clever and effective agents to prevent, mitigate or cure all manner of human ailments, one of the remaining holy grails in biomedicine is drug delivery.

For true in-patient success, drugs need to access their target and do their job without being degraded, diluted or diverted by the body’s natural processes. And without causing adverse side effects that can in some cases be more dangerous than the disease.

Consequently, the massive efforts in drug development research have been paralleled by research focused on targeting, facilitating and even personalising drug delivery systems.

One group in particular that has taken up the delivery challenge is the mix of chemists, engineers, and biologists that make up the group of Professor Frank Caruso from the Department of Chemical and Biomolecular Engineering at The University of Melbourne.

One wouldn’t immediately link one of the top 20 materials scientists in the world (according to Thompsons Reuters, 2011) with the world of biomedicine and cells, but Caruso’s work over the last few years is very much in that space.

“One of the group’s major focuses is designing particle-based delivery systems for a range of biomedical applications that ultimately will lead to more effective medicines, vaccines, and even tissue regeneration strategies.

“To do this, we are developing materials with engineered properties at the nanoscale and impart unique functionalities into our systems. These properties may be biological or they could be a responsive or adaptive property whereby the materials themselves can respond to, for example, specific biological environments.”

Why so small?

As the name suggests, nanotechnology deals with molecules and structures in the nanometer range – from 1 to 100 x 10^-9 metres. Matter behaves very differently at this level, and these emergent properties can be exploited to derive functions that otherwise would not be possible.

“If you then couple nanoengineering principles to biological environments and challenges, a whole new set of possibilities emerges,” says Caruso.

“For instance, we could design or engineer our particles to interact with a cell such that they might specifically degrade only once they get inside that cell, thus releasing the therapeutic agent to the place where it will be most effective.”

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This might avoid a drug or vaccine, for instance, being degraded before it can do its work, resulting in smaller required doses and less side effects. Or, if the released agent is cytotoxic, the particle delivery system could facilitate the target cell being lethally attacked from within without affecting other cells.

We also need to think about targeting the effective or ‘loaded’ particles to specific cells. One such approach being taken by Caruso’s team involves incorporating antibodies onto the surface of the particles.

“In one of our projects, we have obtained a range of antibodies from our collaborators at the Ludwig Cancer Research Institute here in Melbourne. These antibodies are highly selective for colorectal cancer cells, and we know in vitro that we get very high selectivity to the cancerous cells by attaching the antibodies to our particles.”

Caruso’s particle delivery system is reminiscent of Shrek’s onion self-analysis, with many different and surprising layers. Although a lot smaller, of course. “We start with a variety of biodegradable and biocompatible polymers that we design and make or modify using synthetic protocols, and then we assemble them into containers or particles.”

The final assembled containers can be solid colloid particles, or they can be hollow. The solid ones tend to have the drug embedded or incorporated within the matrix, while the hollow particles are literally in-filled with the drug.

Caruso’s team can also tweak the features of the polymer itself to match a specific biological or delivery requirement. For instance, the particle’s surface can be made chemical, temperature or pH-responsive. “Such nano-engineering enables us to manipulate the particles in terms of how much drug can be loaded and how the drug can be released under various biological circumstances.”

Read more about Frank Caruso’s research in Part II, coming soon.