@PhdThesis{diss_mods_00022869, author = {G{\"u}tter, Friederike}, title = {Understanding nano-stabiliser and nano-bio interactions of nanocrystals}, year = {2018}, publisher = {Christian-Albrechts-Universit{\"a}t zu Kiel}, address = {Kiel}, keywords = {nanocrystals nano-bio interactions; Nanokristalle Nano-Bio-Interaktionen}, abstract = {A high percentage of newly developed active pharmaceutical ingredients (APIs) show poor aqueous solubility but high therapeutical efficacy. When an API is poor soluble in water, the absorption is usually low and therefore the therapeutic effect is decreased. For this thesis, with curcumin (CUR) and glibenclamide (GLI), two poor water soluble APIs were selected. A processing to nanocrystals (NCs) was performed. For the production of NCs, the API was suspended in water together with stabiliser(s) (ST) and grinded in a media mill. With all used ST, NC suspensions with particle sizes down to 300 nm could be produced. However, they had different efficacies. To investigate interactions between ST and API, two methods were chosen: isothermal titration calorimetry (ITC) and contact angle measurements (CAM). ITC showed PS80 as a fast adsorbing ST. CAM could be used to forecast the PS80 concentration suitable for stabilisation of GLI. The influence of the ST and the size of the NCs on the permeation of CUR and GLI in bio-relevant environments was investigated in an epithelial cell model. 500 nm NCs had higher permeation rate compared to 300 nm NCs. The influence of the particle size was even more pronounced than the influence of the stabiliser. Fluorescence microscopy and coherent anti-Stokes Raman microscopy were utilised to investigate the uptake of NCs. To investigate the influence of the ST on the uptake of NCs, a macrophage cell line was employed. Next to the influence of the stabiliser also the influence of the particle size and incubation time were examined. The type of stabiliser had the highest influence on uptake of NCs with HPMC+PS80 stabilised NCs giving the highest uptake rates. In this thesis, the substantial influence of the ST could be highlighted. The production, absorption in enterocytes and elimination (through macrophages) of NCs are dependent on the type of ST. Therefore, the selection of ST must be of high priority in the development of nanosuspensions.}, url = {https://macau.uni-kiel.de/receive/diss_mods_00022869}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/dissertation_derivate_00007623/Dissertation_F.Guetter.pdf:PDF}, language = {en} }