Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity.
Adult
Anti-Inflammatory Agents
Cells, Cultured
Dextrans
/ chemistry
Dinoprostone
/ metabolism
Drug Compounding
Fluorescent Dyes
/ chemistry
Humans
Isoxazoles
/ chemistry
Nanoparticles
/ chemistry
Neutrophils
/ drug effects
Polylactic Acid-Polyglycolic Acid Copolymer
/ chemistry
Quinolines
/ chemistry
Acetalated dextran
BRP-187
Dual inhibitor
FLAP inhibitor
Leukotriene biosynthesis
MPGES-1
Nanoparticles
PLGA
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
14 May 2020
14 May 2020
Historique:
received:
26
02
2020
accepted:
19
04
2020
entrez:
16
5
2020
pubmed:
16
5
2020
medline:
26
1
2021
Statut:
epublish
Résumé
Dual inhibitors of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E 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. 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 E
Sections du résumé
BACKGROUND
BACKGROUND
Dual inhibitors of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E
RESULTS
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
CONCLUSIONS
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 E
Identifiants
pubmed: 32408877
doi: 10.1186/s12951-020-00620-7
pii: 10.1186/s12951-020-00620-7
pmc: PMC7227278
doi:
Substances chimiques
Anti-Inflammatory Agents
0
BRP-187
0
Dextrans
0
Fluorescent Dyes
0
Isoxazoles
0
Quinolines
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 316213987
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