| Autor: |
Blerina Shkodra-Pula, Christian Kretzer, Paul M. Jordan, Paul Klemm, Andreas Koeberle, David Pretzel, Erden Banoglu, Stefan Lorkowski, Maria Wallert, Stephanie Höppener, Steffi Stumpf, Antje Vollrath, Stephanie Schubert, Oliver Werz, Ulrich S. Schubert |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal of Nanobiotechnology, Vol 18, Iss 1, Pp 1-14 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1477-3155 |
| DOI: |
10.1186/s12951-020-00620-7 |
| Popis: |
Abstract Background Dual inhibitors of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E2 synthase-1 (mPGES-1) may exert better anti-inflammatory efficacy and lower risks of adverse effects versus non-steroidal anti-inflammatory drugs. Despite these advantages, many dual FLAP/mPGES-1 inhibitors are acidic lipophilic molecules with low solubility and strong tendency for plasma protein binding that limit their bioavailability and bioactivity. Here, we present the encapsulation of the dual FLAP/mPGES-1 inhibitor BRP-187 into the biocompatible polymers acetalated dextran (Acdex) and poly(lactic-co-glycolic acid) (PLGA) via nanoprecipitation. Results The nanoparticles containing BRP-187 were prepared by the nanoprecipitation method and analyzed by dynamic light scattering regarding their hydrodynamic diameter, by scanning electron microscopy for morphology properties, and by UV–VIS spectroscopy for determination of the encapsulation efficiency of the drug. Moreover, we designed fluorescent BRP-187 particles, which showed high cellular uptake by leukocytes, as analyzed by flow cytometry. Finally, BRP-187 nanoparticles were tested in human polymorphonuclear leukocytes and macrophages to determine drug uptake, cytotoxicity, and efficiency to inhibit FLAP and mPGES-1. Conclusion Our results demonstrate that encapsulation of BRP-187 into Acdex and PLGA is feasible, and both PLGA- and Acdex-based particles loaded with BRP-187 are more efficient in suppressing 5-lipoxygenase product formation and prostaglandin E2 biosynthesis in intact cells as compared to the free compound, particularly after prolonged preincubation periods. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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