Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy
Author Department
Pathology
Document Type
Article, Peer-reviewed
Publication Date
10-2024
Abstract
Localized delivery of inflammasome inhibitors in phagocytic macrophages could be promising for psoriasis treatment. The present work demonstrates the development of non-spherical lipid nanoparticles, mimicking pathogen-like shapes, consisting of an anti-inflammatory inflammasome inhibiting lipid (pyridoxine dipalmitate) as a trojan horse. The nanorods inhibit inflammasome by 3.8- and 4.5-fold compared with nanoellipses and nanospheres, respectively. Nanorods reduce apoptosis-associated speck-like protein and lysosomal rupture, restrain calcium influx, and mitochondrial reactive oxygen species. Dual inflammasome inhibitor (NLRP3/AIM-2-IN-3) loaded nanorods cause synergistic inhibition by 21.5- and 59-folds compared with nanorods and free drug, respectively alongside caspase-1 inhibition. The NLRP3/AIM-2-IN-3 nanorod when transformed into a polymeric scaffold, simultaneously and effectively inhibits RNA levels of NLRP3, AIM2, caspase-1, chemokine ligand-2, gasdermin-D, interleukin-1β, toll-like receptor 7/ 8, and IL-17A by 6.4-, 1.6-, 2.0-, 13.0-, 4.2-, 24.4-, 4.3-, and 1.82-fold, respectively in psoriatic skin in comparison to Imiquimod positive control group in an in-vivo psoriasis-like mice model.
Recommended Citation
Surve D, Fish A, Debnath M, Pinjari A, Lorenzana A, Piya S, Peyton S, Kulkarni A. Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy. Nat Commun. 2024 Oct 19;15(1):9035. doi: 10.1038/s41467-024-53396-x.
PMID
39426974