Cyclodextrin- and silica-based carrier systems for theranostic applications

Infectious diseases due to multidrug resistant bacteria are becoming a global health concern. The EU has published her Action Plan in 2011 against the rising threats from antimicrobial resistance. Developing new antibiotics is mandatory but takes years. A short-term alternative is the development of novel strategies to deliver existing drugs in an optimized way. In this frame, the use of antibiotic nanocarriers is one of the most promising options. The objective of our research in the frame of the ITN project Cyclonhit is to take full advantage of nanotechnology to efficiently encapsulate antibiotics in nanocarriers to kill both intracellular and extracellular bacteria. We focused on two drugs, Ethionamide (ETH), a second line drug in the treatment of tuberculosis, and Clofazimine, a drug used in the case of leprosy. Both have severe side effects due to their low therapeutic index and suffer from insolubility in water hampering their administration. We addressed this problem by loading ETH in polymeric ?-cyclodextrin (?CyD)-based carriers and CLZ in fluorescent mesoporous silica particles as well as sulfobutyl ?CyD oligomeric carriers. CLZ was successfully loaded in three types of mesoporous silica particles exhibiting intrinsic fluorescence with long fluorescence lifetimes up to 10 ns.1 The system has very appealing properties for theranostic applications. For both drugs highly improved solubility in water has been obtained with the ?CyD-based polymeric carriers.2-3 The CLZ/ sulfobutyl ?CyD carrier system has very interesting IC50 values in the nanomolar range against MDR S. Epidermidis.