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Sensitive polymers show drug delivery promise


20 March 2009

Chemists in the US have developed a three-component polymer that can respond to temperature, pH and the presence of a reducing agent. This means that when the polymer is made into micelles to encapsulate and deliver drugs, there are three different ways to release them where they are needed. 

Polymeric micelles are nano-sized particles made from clumps of polymer chains with both hydrophobic and hydrophilic ends. In aqueous solutions, the chains come together forming spheres with the hydrophobic end pointing inwards and the hydrophilic ends point outwards - trapping smaller molecules inside the structure. 

Although there are potential uses in nanotechnology, medical imaging and catalysis, the most promising role for these micelles is drug delivery, but it is crucial that they disassemble in the right place to ensure that the drug is released where it is needed. 

Micelle formation and disassembly

The polymer is made up of three components to combine temperature, acid and redox sensitivity

© J. Am. Chem. Soc

Now, Thai Thayumanavan and colleagues at the University of Massachusetts in Amherst, US, have devised a system that responds to three different conditions. 'For better targeting in drug delivery, it is desirable that there is cooperation between multiple stimuli,' Thayumanavan told Chemistry World

The idea, he explains, is to develop a polymer that requires two or more stimuli to release its cargo. Since body chemistry is complex, many drug delivery systems are prone to 'leaking' - so a polymer that responds to multiple conditions would be highly effective. 'We are not sure whether this polymer itself will be a viable drug delivery vehicle,' Thayumanavan adds, but indicates that it is a step in the right direction. 

The new polymer comprises two different polymers joined in the centre by a chemical linker. Poly(N-isopropyl acrylamide) forms the temperature sensitive, hydrophilic end, while 2-hydroxyethyl methacrylate makes up the hydrophobic, pH-sensitive end. Under gentle heating or mildly acidic conditions, the polymers will switch from being hydrophobic to hydrophilic (or vice versa) - causing the micelles to disassemble.

The final part in the sensitivity trio is played by the central linker itself, which contains a disulfide group. This group can easily be cleaved by a mild reducing agent, scissoring the polymer chains apart. 

'This is a really neat piece of work,' says David Fulton, a polymer expert at Newcastle University, UK. 'The trick is to make micelles give up their payload on command, and the group have found a very clever system to do this.' 

Fulton also noted that Thayumanavan's team had found another interesting thing: that a tripeptide found in cells called glutathione can trigger the reduction of the central linker. 'Given that some cancer cells are known to have high concentrations of glutathione, this work holds great promise and could lead to the development of a new class of 'smart' drug delivery systems,' he says. 

Lewis Brindley

 

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References

A Klaikherd et alJACS, 2009. DOI: 10.1021/ja809475a

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