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Optical characterization of potential drugs and drug delivery systemsRosenbaum, Erik January 2011 (has links)
This Thesis is a characterization study on substances having potency as drugs as well as on a lipid based drug-delivery matrix. The optical properties of newly synthesized molecules with proven pilicide properties have been characterized with several spectroscopic methods. These methods include optical absorption and fluorescence as well as time-resolved fluorescence. Upon covalently linking compounds with high quantum yields of fluorescence to specific parts of the pilicide, the biological impact was found to increase for some of the derivatives. Furthermore, by expanding the aromatic part of the pilicide molecule, a significant increase in the inherent fluorescence was obtained. The S0-S1 absorption band for these molecules was found to originate from an impure electronic transition, vibronically promoted by intensity borrowing from higher electronic states. Included in this Thesis is the measurement of how deeply some in this class of newly synthesized molecules become situated when placed inside ganglioside GM1 micelles, and how the molecules’ reorientation is affected. By means of radiation-less energy transfer, it was shown that the molecules place themselves close to the hydrophobic-hydrophilic interface inside the GM1 micelles. As a consequence they are exposed to a densely packed environment, which inhibits the free tumbling of the molecule. This restricted tumbling could be measured by means of time-resolved depolarization experiments. The release of drug-like fluorescent molecules is investigated from a lipid mixture, which upon equilibrium with water forms a mixture of inverted hexagonal and cubic phases. The lipid matrix displayed an extended release over the course of weeks, in vitro, for molecules having a large variation in hydrophobicity.
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