CYCLON

Novel multifunctional cyclodextrin-based nanocarriers for drug encapsulation and delivery as a strategy to overcome current therapeutic drawbacks

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 Obiettivo del progetto (Objective)

'There is a high demand for the development of new drug delivery strategies to combat major diseases in our society, particularly cancer. Current treatments are based on high efficacy drugs, however their non-selective uptake by both normal and tumor cells as well as the development of multidrug resistance (MDR), constitute major hurdles. Resistance is also associated with the use of nucleoside analogues as anticancer drugs in vivo. Photodynamic therapy (PDT), aims at selectively killing neoplastic lesions by the combined action of a photosensitizer and visible light. Passive targeting, involving enhanced permeability and retention effect, allows the accumulation of drugs on tumor sites, and concomitant active targeting with suitable functionalities, constitute properties currently associated with polymeric delivery systems. Cyclodextrins (CDs) are biocompatible and biodegradable oligosaccharide nanocages, known to improve the solubility, stability and bioavailability of drugs. Scattered literature reports incidents that CDs may constitute potential means to overcome certain forms of MDR, or to effectively deliver photosensitizing anticancer drugs preserving their photodynamic properties. This network, highly specialized in CD chemistry, photochemistry, in vitro drug evaluation and in vivo applications, proposes to synthesize diverse families of new CD derivatives to build a platform of CD-based drug delivery nanosystems with a variety of architectures. These new generation nanocarriers, encompassing many cavities in a nm-sized vehicle, will possess high drug loading capacity, improved permeability and retention effect, enhanced targeting and complete biocompatibility. Their mode of action will be assessed in vitro and in vivo. These goals will be achieved via a strong training program of ESRs and ERs in a highly collaborating, multidisciplinary and application oriented program, with full participation of an SME partner, a leader in CD applications.'

Introduzione (Teaser)

New drug delivery strategies are needed to combat diseases. A European consortium resorted to novel sugar-based nanomaterials as drug delivery vehicles.

Descrizione progetto (Article)

The majority of commercially available drugs exhibit high efficacy but poor selectivity as they are unfortunately taken up by non-target cells. This often causes significant side-effects mainly associated with drug cytotoxicity.

Cyclodextrins (CDs) have emerged as benign molecular carriers that improve the stability and bioavailability of administered drugs. The biocompatibility and biodegradability of these oligosaccharide nanocages make them very promising for in vivo administration.

Many reports unveil additional interesting properties of CDs including their ability to overcome certain forms of multidrug resistance. Furthermore, because of their ability to effectively deliver photosensitising anticancer drugs they could be useful in photodynamic therapy (PDT), a new approach that utilises light-controlled delivery.

The EU-funded http://www.itn-cyclon.eu/ (CYCLON) project developed a series of drug delivery nanosystems based on CDs. The design of the cavities facilitates high drug loading capacity, enhances targeting and overall improves permeability and retention.

Diverse families of specifically modified CDs and nanoscale metal-organic frameworks (nanoMOFs) were synthesised with novel architectures fit for different purposes. One such system proved ideal for carrying the anti-HIV AZT drugs into HIV target cells, exhibiting efficient protection against viral infection. The researchers demonstrated that the nanocarriers could maintain the stability of the drug delivery during transfer of doxorubicin to cancer cells. Furthermore the scientists developed nanoparticles that respond to light for the delivery of E. coli targeted bacteriocides.

Overall, the results obtained with the CYCLON drug delivery platforms were very promising, supporting their multifunctionality and versatility. In particular, optically controlled drug release has massive potential. Over 63 publications were produced by CYCLON members; additionally, a NanoPDT international conference was organized in Gothenburg, Sweden.