ApoE-functionalization of nanoparticles for targeted brain delivery-a feasible method for polyplexes?

Autor: Hartl N; Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, 81377, Munich, Germany., Gabold B; Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, 81377, Munich, Germany., Uhl P; Pharmaceutical Technology and Biopharmaceutics, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120, Heidelberg, Germany., Kromer A; Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, 81377, Munich, Germany., Xiao X; State Key Laboratory of Bioreactor Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China., Fricker G; Pharmaceutical Technology and Biopharmaceutics, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120, Heidelberg, Germany., Mier W; Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany., Liu R; State Key Laboratory of Bioreactor Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China., Merkel OM; Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, 81377, Munich, Germany. olivia.merkel@lmu.de.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Jun; Vol. 14 (6), pp. 1660-1677. Date of Electronic Publication: 2023 Dec 12.
DOI: 10.1007/s13346-023-01482-w
Abstrakt: The blood-brain barrier (BBB) poses a major obstacle in the treatment of all types of central nervous system (CNS) diseases. Small interfering RNA (siRNA) offers in principle a promising therapeutic approach by downregulating disease-related genes via RNA interference. However, the BBB is a formidable barrier for macromolecules such as nucleic acids. In an effort to develop a brain-targeted strategy for siRNA delivery systems formed by electrostatic interactions with cationic polymers (polyplexes (PXs)), we investigated the suitability of the well-known surfactant-based approach for Apolipoprotein E (ApoE)-functionalization of nanoparticles (NPs). The aim of this present work was to investigate if ApoE coating of siRNA PXs formed with cationic branched 25-kDa poly(ethyleneimine) (b-PEI) and nylon-3 polymers without or after precoating with polysorbate 80 (PS 80) would promote successful delivery across the BBB. We utilized highly hydrophobic NM 0.2 /CP 0.8 nylon-3 polymers to evaluate the effects of hydrophobic cyclopentyl (CP) subunits on ApoE binding efficacy and observed successful ApoE binding with and without PS 80 precoating to the nylon-3 but not the PEI polyplexes. Accordingly, ApoE-coated nylon-3 polyplexes showed significantly increased uptake and gene silencing in U87 glioma cells but no benefit in vivo. In conclusion, further optimization of ApoE-functionalized polyplexes and more sophisticated in vitro models are required to achieve more successful in vitro-in vivo translation in future approaches.
(© 2023. The Author(s).)
Databáze: MEDLINE
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