Opposites attract - Building cationic nanocarriers for anionic drugs.

neutrons were used to study potential cationic nanocarriers

neutrons were used to study potential cationic nanocarriers
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Nanotechnology is all about little things with a big impact. From constantly shrinking electronic components, with as much processing power as a supercomputer, to nanosized systems to diagnose or treat disease - nanomaterials can offer creative solutions to big problems. In a recent study, scientists from the University of Greenwich, University of Barcelona, and The institute for Advanced Chemistry of Catalonia, INL and ISIS have used neutrons to study potential cationic nanocarriers and their interaction with anionic drugs.

Putting the Nano into Nanocarrier

Nanocarriers are special couriers for delivering drugs. In order to be effective, they need to be soluble in the biological environment of the human body whilst being able to interact with and carry a specific drug. Nanocarriers also need to have a high stability so that they remain independent of each other and don’t stick together.

Nanocarriers can be built from tiny molecules called surfactants. Surfactants are amphiphiles - they have a water-attracting head component and a fat-attracting tail component. These surfactants can come together to form small injectable balls called micelles in which the heads of the surfactants protrude into the water phase and the hydrocarbon tails point inwards to exclude water. These micelles are soluble in the body and can encapsulate drugs.

Scientists are interested in the ability to tailor the surfactant shell of the capsule in order to allow the optimisation and targeted delivery of drugs – a system that offers many advantages for treatment of diseases such as cancer where toxic chemotherapeutic agents need to be directed specifically to a tumour whilst avoiding healthy tissue.

Crucially many of the drugs that can improve our life quality are anionic; they have a negative charge. This has sparked scientists to investigate the use of positively charged or cationic molecules coupled with soluble surfactant molecules in order to generate cationic micelles that interact with and carry these anionic drugs to their destination in the body.

Prof. Peter Griffiths, University of Greenwich explains “We are interested in synthesizing and studying the behavior of positively charged molecules with the capability of detecting and interacting with negatively charged molecules. The negatively charged molecules of interest are those of biological and environmental importance. For this reason, the positively charged molecules must be soluble in water and exhibit the desired properties in this solvent. Our final goal is to develop systems that could act as very small molecule carriers for drugs or biosensors”

Neutrons demonstrate a new potential Nanocarrier for drugs.

Peter and his team constructed the nanocarriers using dicationic Gemini surfactants based on Bis-imidazolium salts; Gemini surfactants are slightly different to conventional surfactants in that they have two head groups and two tail groups often connected by a rigid spacer. These properties enhance Gemini surfactants capability to build blocks for nanocarriers. The team used a combination of techniques including small angle neutron scattering to study the structure of the micelles formed and to quantify the interaction between a model anionic drug valproate and this carrier.

Peter and his team constructed the nanocarriers.

Peter and his team constructed the nanocarriers using dicationic Gemini surfactants based on Bis-imidazolium salts. They then looked at the interaction with anionic drugs such as valproate.
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Prof. Griffiths explains “We used tensiometry, fluorescence spectrophotometry and pulsed-gradient spin echo (PGSE-NMR) techniques to assess the ability of the dicationic amphiphilic molecules, based on bis-imidazolium salts, to self-assemble. These experiments indicated that the molecules self-assembled into aggregates but with no detailed evidence of micelle formation. In order to probe the type of aggregates formed we needed a technique that would allow is to resolve at the small length scale whilst giving us information on the type, morphology and dimensions of the aggregates in the presence and absence of the drug - That’s were neutron scattering came in.”

The results of the study were very promising and revealed the capacity of these dicationic bis-imidazolium amphiphiles to interact with the anionic drug studied and act as nanocarriers in water. It was also determined that the valproate boosted the micelle formation.

Prof. Griffiths explains “The neutron data revealed the final key evidence of micelle formation and showed molecules with longer hydrocarbon tails formed better defined aggregates than those from shorter molecules. We also found that the presence of the rigid spacer in Gemini surfactants boosted the micelle formation capacity. Most excitingly after combining the neutron data with the results from the PGSE-NMR we were also able to quantify the surfactant drug interaction.”

Further complementary toxicity and clinic studies will be crucial to ensure the feasibility of using these systems in drug delivery however the development of nanocarriers with proven ability to detect anions holds much promise for future biomedical applications.

                                                                                            Felice Laake

Lucía Casal-Dujat et al.

Research date: October 2013

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