Investigation of supersaturated and solubilising preparations of poorly water-soluble photosensitisers intended for antimicrobial photodynamic therapy: Natural deep eutectic solvents and solid dispersions
نویسنده
چکیده
.......................................................................................................................................... 2 List of publications ......................................................................................................................... 3 Abbreviations .................................................................................................................................. 4 1. Aim of the project.................................................................................................................... 5 2. Introduction ............................................................................................................................. 6 2.1. Photoreactivity of a drug substance ................................................................................. 7 2.2. Antimicrobial photodynamic therapy............................................................................... 8 2.3. Formulation of products intended for topical aPDT ...................................................... 11 2.4. Model photoreactive drug substances ............................................................................ 12 2.4.1. Curcumin........................................................................................................................ 12 2.4.2. Porphyrins ...................................................................................................................... 15 2.5. Cyclodextrins as solubility enhancers ............................................................................ 18 2.6. Eutectic solvents............................................................................................................. 20 2.6.1. Natural deep eutectic solvents ........................................................................................ 22 2.6.2. Natural deep eutectic solvents as solvents for photoreactive drugs intended for aPDT 23 2.7. Supersaturating drug delivery systems intended for topical aPDT ................................ 27 3. Summary of papers ................................................................................................................ 30 Paper I ....................................................................................................................................... 30 Paper II ...................................................................................................................................... 31 Paper III ..................................................................................................................................... 31 Paper IV..................................................................................................................................... 32 Paper V ...................................................................................................................................... 33 4. General experimental conditions ........................................................................................... 35 4.1. Materials......................................................................................................................... 35 4.2. Curcumin solid dispersions ............................................................................................ 37 4.2.1. Complexation between curcumin and M CD ................................................................ 37 4.2.2. Preparation of curcumin solid dispersions ..................................................................... 37 4.2.3. Solid state characterisation of curcumin solid dispersions............................................. 39 4.2.4. Characterisation of the dissolved lyophilisates .............................................................. 39 4.3. NADES as solvents for PSs ........................................................................................... 40 4.3.1. Preparation of PS-NADES ............................................................................................. 40 4.3.2. Characterisation of the pure NADES ............................................................................. 40 4.3.3. Viscosity measurements of NADES (only reported in the thesis) ................................. 42 4.3.4. Solubility of PSs in NADES .......................................................................................... 42 4.3.5. Characterisation of PS-NADES samples ....................................................................... 43 4.4. Bacterial (photo-) toxicity studies .................................................................................. 43 4.4.1. The light source .............................................................................................................. 44 4.5. Investigation of the antimicrobial effect of NADES...................................................... 45 5. Main results and discussion................................................................................................... 46 5.1. Preparations of curcumin ............................................................................................... 46 5.1.1. Curcumin complexation with cyclodextrin .................................................................... 46 5.1.2. Characterisation of curcumin solid dispersions ............................................................. 47 5.1.3. Curcumin solubilisation in NADES ............................................................................... 49 5.1.4. Curcumin drug delivery systems dissolved in aqueous solution ................................... 51 5.1.5. Hydrolytic stability of curcumin in diluted NADES ...................................................... 54 5.1.6. In vitro bacterial phototoxicity of curcumin preparations .............................................. 55 5.2. Model porphyrin photosensitisers solubilised in NADES ............................................. 57 5.2.1. Characterisation of porphyrins solubilised in NADES .................................................. 60 5.2.2. Solubilisation of model porphyrins in diluted NADES ................................................. 61 5.2.3. In vitro bacterial phototoxicity of model porphyrins in NADES ................................... 64 5.3. Investigation of the antimicrobial effect of NADES...................................................... 69 5.4. Are NADES suitable as solvents for photosensitisers in aPDT? ................................... 72 5.4.1. Osmolality of diluted NADES ....................................................................................... 73 5.4.2. Viscosity of undiluted and diluted NADES ................................................................... 75 6. Concluding remarks............................................................................................................... 77 7. Future perspectives ................................................................................................................ 79 References ..................................................................................................................................... 80
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تاریخ انتشار 2017