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Immune Modifying Effect of Drug Free Biodegradable Nanoparticles on Disease Course of Experimental Autoimmune Neuritis

ORCID
0000-0002-7526-6730
Affiliation
Department of Neurology, University Clinic Bonn, Campus Venusberg 1, 53127 Bonn, Germany
Elahi, Ehsan;
ORCID
0000-0003-2755-9616
Affiliation
Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk Str. 3, 53121 Bonn, Germany
Ali, Mohamed Ehab;
Affiliation
Department of Neurology, University Clinic Bonn, Campus Venusberg 1, 53127 Bonn, Germany
Zimmermann, Julian;
Affiliation
Myeloid Therapeutics, 300 Technology Sq., Suite 203, Cambridge, MA 02139, USA
Getts, Daniel R.;
Affiliation
Department of Neurology, University Clinic Bonn, Campus Venusberg 1, 53127 Bonn, Germany
Müller, Marcus;
Affiliation
Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk Str. 3, 53121 Bonn, Germany
Lamprecht, Alf

Guillain-Barré Syndrome (GBS) is an autoimmune disease of demyelination and inflammation of peripheral nerves. Current treatments are limited to plasma exchange and intravenous immunoglobulins. Cargo-free nanoparticles (NPs) have been evaluated here for their therapeutic benefit on the disease course of experimental autoimmune neuritis (EAN), mimicking the human GBS. NPs prepared from poly-lactic co-glycolic acid (PLGA) with variable size and surface charge (i.e., 500 nm vs. 130 nm, polyvinyl alcohol (PVA) vs. sodium cholate), were intravenously administered in before- or early-onset treatment schedules in a rat EAN model. NP treatment mitigated distinctly the clinical severity of EAN as compared to the P2-peptide control group (P2) in all treatments and reduced the trafficking of inflammatory monocytes at inflammatory loci and diverted them towards the spleen. Therapeutic treatment with NPs reduced the expression of proinflammatory markers (CD68 (P2: 34.8 ± 6.6 vs. NP: 11.9 ± 2.3), IL-1β (P2: 18.3 ± 0.8 vs. NP: 5.8 ± 2.2), TNF-α (P2: 23.5 ± 3.7 vs. NP: 8.3 ± 1.7) and elevated the expression levels of anti-inflammatory markers CD163 (P2: 19.7 ± 3.0 vs. NP: 41.1 ± 6.5; all for NP-PVA of 130 nm; relative to healthy control). These results highlight the therapeutic potential of such cargo-free NPs in treating EAN, which would be easily translatable into clinical use due to their well-known low-toxicity profile.

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