April 14, 2008
Supramolecular Chemistry for Drug Delivery

Bucket-shaped molecules known as cyclodextrins are well-known for their unique ability to act as molecular containers by entrapping guest molecules in their internal cavity. Cyclodextrins are used as solubilisers in pharmaceutics as they can include small less-soluble drug molecules within their own large molecular cavities and thus improve their bioavailability.

As a result of their unique structure, these molecules have found applications in environmental protection, by immobilising toxic compounds inside their rings, and in the food industry for the preparation of cholesterol-free products and for stabilising volatile or unstable compounds and reducing unwanted tastes and odours.

Image of a simulated micelle above a landscape of real vesicles
Image of a simulated micelle formed by amphiphilic cyclodextrin molecules
above a landscape of real cyclodextrin vesicles

Poor binding constants however have made transport and targeting of drugs by cyclodextrins an unrealistic prospect, although one much hyped in the literature. But cyclodextrins developed by Dr Raphael Darcy and co-workers in the UCD School of Chemistry and Chemical Biology are designed to assemble in solution; they assemble into what might be called minimalist cells.

According to Dr Darcy: "With their aqueous interiors and receptor exteriors, the assemblies open new prospects for drug delivery. The mesomolecular size range enables complex formation with oligonucleotides for prospective gene therapy."

A review on supramolecular chemistry for drug delivery by Dr Florence Sallas, currently a post-doctoral researcher at the CSCB, and Dr Darcy, researcher emeritus at the CSCB, has been highlighted on the cover of a recent issue of the European Journal of Organic Chemistry. The image shows a simulated micelle formed by amphiphilic cyclodextrin molecules above a landscape of real cyclodextrin vesicles. The review, entitled 'Amphiphilic cyclodextrins – advances in synthesis and supramolecular chemistry' is available here.

Such supramolecular biotechnology, including DNA or RNA delivery, is a main theme in the Irish Drug Delivery Research Network, established in December 2007 with the award of €5.2M from Science Foundation Ireland (SFI). This Cluster led by Professor David Brayden, UCD School of Agriculture, Food Science and Veterinary Medicine, brings together the major drug delivery research groups from UCD’s Conway Institute, the CSCB and from Ireland’s three Schools of Pharmacy based at UCC, TCD and RCSI. Additional support was obtained from industrial partners Genzyme Ireland (Waterford), Sigmoid Biotechnologies (Dublin) and Warwick Effect Polymers (Coventry, UK).

The Cluster will investigate how a selection of novel formulations of polymers can be used to promote oral and inhaled delivery of biotech molecules that normally have to be injected (e.g. insulin) or molecules that cannot be delivered to the body in an acceptable format by any route of delivery (e.g. genes).

For the first time the three Schools of Pharmacy will be combining resources in drug delivery. Chemistry expertise is being supplied by UCD and RCSI, namely by CSCB principal investigators Dr Raphael Darcy, UCD, and Dr Marc Devocelle, RCSI. 12 PhD students and 6 postdoctoral workers will be hired in the Cluster's first two years.

 

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