Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy

Dhanashree Surve, Adam Fish, Maharshi Debnath, Aniruddha Pinjari, Adrian Lorenzana, Sumi Piya, Shelly Peyton and Ashish Kulkarni ()
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Dhanashree Surve: University of Massachusetts
Adam Fish: University of Massachusetts
Maharshi Debnath: University of Massachusetts
Aniruddha Pinjari: University of Massachusetts
Adrian Lorenzana: University of Massachusetts
Sumi Piya: Baystate Medical Center
Shelly Peyton: University of Massachusetts
Ashish Kulkarni: University of Massachusetts

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53396-x

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