Unknown

Dataset Information

0

Development of therapeutic polymeric nanoparticles for the resolution of inflammation.


ABSTRACT: Liver X receptors (LXRs) attenuate inflammation by modulating the expression of key inflammatory genes, making LXRs and their ligands particularly attractive candidates for therapeutic intervention in cardiovascular, metabolic, and/or inflammatory diseases. Herein, enhanced proresolving activity of polymeric nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs) is demonstrated, developed from a combinatorial library of more than 70 formulations with variations in critical physicochemical parameters. In vitro studies on peritoneal macrophages confirm that LXR-NPs are significantly more effective than the free agonist at downregulating pro-inflammatory mediators (MCP-1 and TNF?), as well as inducing the expression of LXR target genes (ABCA1 and SREBP1c). Through a zymosan-induced acute peritonitis in vivo model, LXR-NPs are found to be more efficient than free GW3965 at limiting the recruitment of polymononuclear neutrophils (50% vs 17%), suppressing the gene expression and secretion of pro-inflammatory factors MCP-1 and TNF? in peritoneal macrophages, and decreasing the resolution interval up to 4 h. Furthermore, LXR-NPs suppress the secretion of MCP-1 and TNF? by monocytes and macrophages more efficiently than the commercial drug dexamethasone. Overall, these findings demonstrate that LXR-NPs are capable of promoting resolution of inflammation and highlight the prospect of LXR-based nanotherapeutics for inflammatory diseases.

SUBMITTER: Gadde S 

PROVIDER: S-EPMC4160375 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications


Liver X receptors (LXRs) attenuate inflammation by modulating the expression of key inflammatory genes, making LXRs and their ligands particularly attractive candidates for therapeutic intervention in cardiovascular, metabolic, and/or inflammatory diseases. Herein, enhanced proresolving activity of polymeric nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs) is demonstrated, developed from a combinatorial library of more than 70 formulations with variations in critical phy  ...[more]

Similar Datasets

| S-EPMC3684255 | biostudies-other
| S-EPMC3631648 | biostudies-literature
| S-EPMC4486355 | biostudies-literature
| S-EPMC4143165 | biostudies-literature
| S-EPMC4835185 | biostudies-literature
| S-EPMC5496926 | biostudies-literature
| S-EPMC9951517 | biostudies-literature
| S-EPMC4525301 | biostudies-literature
| S-EPMC8568333 | biostudies-literature
2023-08-01 | GSE239411 | GEO