@article{LiStoecklLukasetal.2021,
  author    = {Li, Shushan and St{\"o}ckl, Sabine and Lukas, Christoph and Herrmann, Marietta and Brochhausen, Christoph and K{\"o}nig, Matthias A. and Johnstone, Brian and Gr{\"a}ssel, Susanne},
  title     = {Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p},
  series = {Stem Cell Research \& Therapy},
  volume    = {12},
  journal   = {Stem Cell Research \& Therapy},
  doi       = {10.1186/s13287-021-02317-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364237},
  year      = {2021},
  abstract  = {Background Curcumin has anti-inflammatory effects and qualifies as a potential candidate for the treatment of osteoarthritis (OA). However, curcumin has limited bioavailability. Extracellular vesicles (EVs) are released by multiple cell types and act as molecule carrier during intercellular communication. We assume that EVs can maintain bioavailability and stability of curcumin after encapsulation. Here, we evaluated modulatory effects of curcumin-primed human (h)BMSC-derived EVs (Cur-EVs) on IL-1β stimulated human osteoarthritic chondrocytes (OA-CH). Methods CellTiter-Blue Viability- (CTB), Caspase 3/7-, and live/dead assays were used to determine range of cytotoxic curcumin concentrations for hBMSC and OA-CH. Cur-EVs and control EVs were harvested from cell culture supernatants of hBMSC by ultracentrifugation. Western blotting (WB), transmission electron microscopy, and nanoparticle tracking analysis were performed to characterize the EVs. The intracellular incorporation of EVs derived from PHK26 labeled and curcumin-primed or control hBMSC was tested by adding the labeled EVs to OA-CH cultures. OA-CH were pre-stimulated with IL-1β, followed by Cur-EV and control EV treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay). Relative expression of selected anabolic and catabolic genes was assessed with qRT-PCR. Furthermore, WB was performed to evaluate phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in OA-CH. The effect of hsa-miR-126-3p expression on IL-1β-induced OA-CH was determined using CTB-, Caspase 3/7-, live/dead assays, and WB. Results Cur-EVs promoted viability and reduced apoptosis of IL-1β-stimulated OA-CH and attenuated IL-1β-induced inhibition of migration. Furthermore, Cur-EVs increased gene expression of BCL2, ACAN, SOX9, and COL2A1 and decreased gene expression of IL1B, IL6, MMP13, and COL10A1 in IL-1β-stimulated OA-CH. In addition, phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK, induced by IL-1β, is prevented by Cur-EVs. Cur-EVs increased IL-1β-reduced expression of hsa-miR-126-3p and hsa-miR-126-3p mimic reversed the effects of IL-1β. Conclusion Cur-EVs alleviated IL-1β-induced catabolic effects on OA-CH by promoting viability and migration, reducing apoptosis and phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK thereby modulating pro-inflammatory signaling pathways. Treatment of OA-CH with Cur-EVs is followed by upregulation of expression of hsa-miR-126-3p which is involved in modulation of anabolic response of OA-CH. EVs may be considered as promising drug delivery vehicles of curcumin helping to alleviate OA.},
  language  = {en}
}
@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}
}
@article{LuebtowMarciniakSchmiedeletal.2019,
  author    = {L{\"u}btow, Michael M. and Marciniak, Henning and Schmiedel, Alexander and Roos, Markus and Lambert, Christoph and Luxenhofer, Robert},
  title     = {Ultra-high to ultra-low drug loaded micelles: Probing host-guest interactions by fluorescence spectroscopy},
  series = {Chemistry - A European Journal},
  volume    = {25},
  journal   = {Chemistry - A European Journal},
  number    = {54},
  doi       = {10.1002/chem.201902619},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206128},
  pages     = {12601-12610},
  year      = {2019},
  abstract  = {Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.\%, while the other allows a drug loading of only 25 wt.\%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.},
  subject      = {Polymer-drug interaction},
  language  = {en}
}