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.
Field of science
- /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance/multidrug resistance
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