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Role of CycloLab: Coordinator STUDIES ON THE CYCLODEXTRIN MEMBRANE INTERACTIONS FOR THE DEVELOPMENT OF SECOND GENERATION CYCLODEXTRIN DERIVATIVES TO IMPROVE THE DRUG ABSORPTION The aim of the proposed research is to gain deeper understanding into the interactions between cyclodextrin derivatives and cell membranes and utilising the acquired knowledge to develop new drug formulations, which will potentiate the absorption of the drugs. For these new formulations novel, so called second-generation cyclodextrin derivatives will be developed which will likely enhance the intestinal drug absorption without causing cytotoxicity. Based on our preliminary results, we assume that the drug absorption is enhanced by cyclodextrins by a dual mechanism: increased solubility and inhibition of ABC transporters located in the luminal membrane of the intestinal epithelial cells, known to efflux a variety of drugs. This effect is especially relevant to the low solubility, hydrophobic drugs. We want to study this mechanism using the most up-to-date methods of molecular biology as well as to find and prepare the proper second generation cyclodextrin derivatives. This novel approach that is based on affecting the ABC transporters may contribute to (i) gaining more insights into the interaction of ABC transporters with the membrane lipid environment, (ii) providing data at a molecular level on the modulation of ABC transporter activity by cyclodextrins, (iii) and pointing at a promising new strategy for drug formulation. COORDINATOR |
