2024-11-13 マサチューセッツ大学アマースト校
<関連情報>
- https://www.umass.edu/news/article/new-sprayable-psoriasis-drug-delivery-system-invented-umass-researchers
- https://www.nature.com/articles/s41467-024-53396-x
乾癬治療のための高分子足場における噴霧可能なインフラマソーム阻害脂質ナノロッド 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 & Ashish Kulkarni
Nature Communications Published:19 October 2024
DOI:https://doi.org/10.1038/s41467-024-53396-x
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.
