Aging/Immunosenescence
Strategies to overcome age-related immunosenescence
Immunosenescence is the state of deteriorated immune response to pathogens, associated with the elevated release of inflammatory markers and vulnerability to diseases such as autoimmune disorders and cancer. Drug delivery systems (DDS) provide versatile benefits for treating age-linked diseases, including improved efficacy, cell- or organ-specific transportation, increased absorption, reduced side effects, and controlled drug release. In this set of projects, we aim to shed light on how aging and immunosenescence affect the function of DDS in various immune cells such as macrophages, monocytes, dendritic cells, T cells, B cells, and neutrophils. Furthermore, we aim to develop strategies for immune cell-specific delivery and senescence-specific release of senotherapeutics by particulate DDS.
We draw on a long-lasting experience with polymer-based particulate carriers for immunomodulators, which can be combined with our immunologically inert particles by surface-coating or encapsulation. We also studied the effects of materials, particle sizes, and particle shapes, and have included a range of reporter cell lines and several types of primary human cells in our investigations.
Examples of publications on particulate carriers for cellular uptake and cell modulation:
S. Baudis, T. Roch, M. Balk, C. Wischke, A. Lendlein, M. Behl. Multivariate Analysis of Cellular Uptake Characteristics for a (Co)polymer Particle Library, ACS Biomater. Sci. Eng. 2024, 10, 3, 1481–1493; https://doi.org/10.1021/acsbiomaterials.3c01803
F. Friess, T. Roch, B. Seifert, A. Lendlein, C. Wischke. Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(ε-caprolactone). Int J Pharm, 567 (2019), 118461. https://dx.doi.org/10.1016/j.ijpharm.2019.118461
S. Mathew, A. Lendlein, C. Wischke, Characterization of protein-adjuvant coencapsulation in microparticles for vaccine delivery, Eur J Pharm Biopharm, 87 (2014), 403-407. http://dx.doi.org/10.1016/j.ejpb.2014.04.003
C. Wischke, A. Kruger, T. Roch, B.F. Pierce, W. Li, F. Jung, A. Lendlein, Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio, Eur J Pharm Biopharm, 84 (2013), 288-296. https://pubmed.ncbi.nlm.nih.gov/23429231/
S. Schmidt, T. Roch, S. Mathew, N. Ma, C. Wischke, A. Lendlein, Correlating the Uptake and Dendritic Cell Activation by MDP-loaded Microparticles, Mater Res Soc Symp Proc, 1569 (2013), 179- 184. https://link.springer.com/article/10.1557%2Fopl.2013.816
C. Wischke, S. Mathew, T. Roch, M. Frentsch, A. Lendlein, Potential of NOD receptor ligands as immunomodulators in particulate vaccine carriers, J Control Release, 164 (2012) 299-306. This article was highlighted on the cover of the journal. http://dx.doi.org/10.1016/j.jconrel.2012.06.034
S. Mathew, T. Roch, M. Frentsch, A. Lendlein, C. Wischke, Adjuvant effect of microencapsulated NOD ligands studied in a human phagocytic cell line, J Appl Biomat Funct Mat, 10 (2012) 220-236. http://dx.doi.org/10.5301/JABFM.2012.10438
C. Wischke, J. Zimmermann, B. Wessinger, A. Schendler, H.H. Borchert, J.H. Peters, T. Nesselhut, D.R. Lorenzen, Poly(I:C) coated PLGA microparticles induce dendritic cell maturation, Int J Pharm, 365 (2009) 61-68. http://dx.doi.org/10.1016/j.ijpharm.2008.08.039
C. Wischke, D. Lorenzen, J. Zimmermann, H.H. Borchert, Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for the antigen delivery to dendritic cells using a static micromixer, Eur J Pharm Biopharm, 62 (2006) 247-253. DOI: 10.1016/j.ejpb.2005.08.015
C. Wischke, H.H. Borchert, J. Zimmermann, I. Siebenbrodt, D.R. Lorenzen, Stable cationic microparticles for enhanced model antigen delivery to dendritic cells, J Control Release, 114 (2006) 359-368. DOI: 10.1016/j.jconrel.2006.06.020
C. Wischke, H.H. Borchert, Influence of the primary emulsification procedure on the characteristics of small protein-loaded PLGA microparticles for antigen delivery, J Microencapsul, 23 (2006) 435-448. DOI: 10.1080/02652040600612512