TY - JOUR A1 - Prokopovic, Vladimir Z. A1 - Duschl, Claus A1 - Volodkin, Dmitry T1 - Hyaluronic Acid/Poly-l-Lysine Multilayers as Reservoirs for Storage and Release of Small Charged Molecules JF - Macromolecular bioscience N2 - Polyelectrolyte multilayer films are nowadays very attractive for bioapplications due to their tunable properties and ability to control cellular response. Here we demonstrate that multilayers made of hyaluronic acid and poly-l-lysine act as high-capacity reservoirs for small charged molecules. Strong accumulation within the film is explained by electrostatically driven binding to free charges of polyelectrolytes. Binding and release mechanisms are discussed based on charge balance and polymer dynamics in the film. Our results show that transport of molecules through the film-solution interface limits the release rate. The multilayers might serve as an effective platform for drug delivery and tissue engineering due to high potential for drug loading and controlled release. KW - diffusion KW - drug delivery KW - dye KW - release mechanism Y1 - 2015 U6 - https://doi.org/10.1002/mabi.201500093 SN - 1616-5187 SN - 1616-5195 VL - 15 IS - 10 SP - 1357 EP - 1363 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Löpfe, Moira A1 - Duss, Anja A1 - Zafeiropoulou, Katerina-Alexandra A1 - Bjoergvinsdottir, Oddny A1 - Eglin, David A1 - Fortunato, Giuseppino A1 - Klasen, Jürgen A1 - Ferguson, Stephen J. A1 - Würtz-Kozak, Karin A1 - Krupkova, Olga T1 - Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc JF - Pharmaceutics N2 - Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use. KW - degenerative disc disease KW - inflammation KW - drug delivery KW - EGCG KW - microparticles KW - injectable biomaterial KW - electrospraying Y1 - 2019 U6 - https://doi.org/10.3390/pharmaceutics11090435 SN - 1999-4923 VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Rancan, Fiorenza A1 - Volkmann, Hildburg A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Stanko, Jessica Isolde A1 - Kleuser, Burkhard A1 - Blume-Peytavi, Ulrike A1 - Calderon, Marcelo A1 - Vogt, Annika T1 - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels JF - Pharmaceutics : Molecular Diversity Preservation International N2 - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions. KW - tacrolimus formulation KW - nanogels KW - skin penetration KW - drug delivery KW - human excised skin KW - Jurkat cells Y1 - 2019 U6 - https://doi.org/10.3390/pharmaceutics11080394 SN - 1999-4923 VL - 11 IS - 8 PB - MDPI CY - Basel ER -