Encapsulation of the Anti-inflammatory Dual FLAP/sEH Inhibitor Diflapolin Improves the Efficiency in Human Whole Blood
| Autor: | Christian Kretzer, Stephanie Hoeppener, Dagmar Fischer, Christian Grune, Stephanie Zergiebel, Oliver Werz, Sven Kattner, Jana Thamm |
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| Rok vydání: | 2022 |
| Předmět: |
Drug Carriers
Biocompatibility Dimethyl sulfoxide Anti-Inflammatory Agents Pharmaceutical Science Combinatorial chemistry Polyethylene Glycols chemistry.chemical_compound Drug Delivery Systems chemistry In vivo Drug delivery Lipophilicity Animals Humans Nanoparticles Nanomedicine Female Particle Size Chickens Ethylene glycol Whole blood |
| Zdroj: | Journal of Pharmaceutical Sciences. 111:1843-1850 |
| ISSN: | 0022-3549 |
| Popis: | Diflapolin is a dual FLAP/sEH inhibitor with potent anti-inflammatory efficiency in cellular assays and experimental in vivo studies. Despite these outstanding characteristics, its high lipophilicity and plasma protein binding hamper the bioactivity in blood. To overcome these limitations, diflapolin was encapsulated in poly(lactic-co-glycolic acid) nanoparticles to develop an efficient and biocompatible drug delivery system. Two different cosolvent approaches were tested showing the possibility to exchange dimethyl sulfoxide in the organic phase by the sustainable 400 g/mol poly(ethylene glycol). A particle size of 220 nm and the amorphous encapsulation of diflapolin in high amounts rendered the nanoparticles appropriate for the intended application. Excellent biocompatibility of the nanoparticles was demonstrated in an ex ovo hen's egg model. The potent suppression of FLAP-dependent 5-lipoxygenase product formation by the nanoparticles in human whole blood, superior to the free drug, makes them to a promising drug delivery system to improve the bioactivity of diflapolin. |
| Databáze: | OpenAIRE |
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