@article{LuebtowLorsonFingeretal.2020, author = {L{\"u}btow, Michael M. and Lorson, Thomas and Finger, Tamara and Gr{\"o}ber-Becker, Florian-Kai and Luxenhofer, Robert}, title = {Combining Ultra-High Drug-Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release}, series = {Macromolecular Chemistry and Physics}, volume = {221}, journal = {Macromolecular Chemistry and Physics}, number = {1}, doi = {10.1002/macp.201900341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208115}, pages = {1900341}, year = {2020}, abstract = {Hydrogel-based drug depot formulations are of great interest for therapeutic applications. While the biological activity of such drug depots is often characterized well, the influence of incorporated drug or drug-loaded micelles on the gelation properties of the hydrogel matrix is less investigated. However, the latter is of great importance from fundamental and application points of view as it informs on the physicochemical interactions of drugs and water-swollen polymer networks and it determines injectability, depot stability, as well as drug-release kinetics. Here, the impact of incorporated drug, neat polymer micelles, and drug-loaded micelles on the viscoelastic properties of a cytocompatible hydrogel is investigated systematically. To challenge the hydrogel with regard to the desired application as injectable drug depot, curcumin (CUR) is chosen as a model compound due to its very low-water solubility and limited stability. CUR is either directly solubilized by the hydrogel or pre-incorporated into polymer micelles. Interference of CUR with the temperature-induced gelation process can be suppressed by pre-incorporation into polymer micelles forming a binary drug delivery system. Drug release from a collagen matrix is studied in a trans-well setup. Compared to direct injection of drug formulations, the hydrogel-based systems show improved and extended drug release over 10 weeks.}, language = {en} } @phdthesis{Luebtow2020, author = {L{\"u}btow, Michael M.}, title = {Structure-property relationships in poly(2-oxazoline)/poly(2-oxazine) based drug formulations}, doi = {10.25972/OPUS-19338}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193387}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {According to estimates, more than 40\% of all new chemical entities developed in pharmaceutical industry are practically insoluble in water. Naturally, the demand for excipients which increase the water solubility and thus, the bioavailability of such hydrophobic drugs is enormous. Poly(2-oxazoline)s (POx) are currently intensively discussed as highly versatile class of biomaterials. Although selected POx based micellar drug formulations exhibit extraordinarily high drug loadings > 50 wt.\% enabling high anti-tumor efficacies in vivo, the formulation of other hydrophobic compounds has failed. This casts doubt on the general understanding in which a hydrophobic active pharmaceutical ingredient is dissolved rather unspecifically in the hydrophobic core of the micelles following the fundamental concept of "like dissolves like". Therefore, a closer look at the interactions between all components within a formulation becomes increasingly important. To do so, a large vehicle platform was synthesized, loaded with various hydrophobic drugs of different structure, and the formulations subsequently characterized with conventional and less conventional techniques. The obtained in-depth insights helped to develop a more thorough understanding about the interaction of polymer and incorporated API finally revealing morphologies deviating from a classical core/shell structure. During these studies, the scarcely investigated polymer class of poly(2-oxazine)s (POzi) was found as promising drug-delivery vehicle for hydrophobic drugs. Apart from this fundamental research, the anti-tumor efficacy of the two APIs curcumin and atorvastatin has been studied in more detail. To increase the scope of POx and POzi based formulations designed for intravenous administration, a curcumin loaded hydrogel was developed as injectable drug-depot.}, subject = {Polymere}, language = {en} }