Large- and Small-Animal Studies of Safety, Pharmacokinetics, and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs

• DOI: 10.1021/acsptsci.4c00068
• Publication Date: 2024-03-21T12:37:56Z
• Authors: Sydney Risen; Sadhana Sharma; Vincenzo S. Gilberto; Stephen Brindley; Mikayla Aguilar; Jared M. Brown; Anushree Chatterjee; Julie A. Moreno; Prashant Nagpal
• Keywords: Biodistribution; Animal model

Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids can offer limited relief for systemic inflammation some organs, many patients never achieve remission, such drugs do not cross the blood-brain barrier, making them ineffective tackling neuroinflammation. Especially brain, unintended activation microglia astrocytes hypothesized to be directly indirectly responsible sclerosis, amyotrophic lateral Parkinson's Alzheimer's disease. Recent studies have also shown that targeting inflammasomes specific immune targets beneficial these diseases. Furthermore, our previous NF-κB NLRP3 through brain penetrant Nanoligomer cocktail SB_NI_112 (abbreviated as NI112) therapeutic several neurodegenerative Here, we show safety-toxicity studies, followed by pharmacokinetics biodistribution small- (mice) large-animal (dog) this inflammasome-targeting NI112. We conducted using four different routes administration: intravenous, subcutaneous, intraperitoneal, intranasal, identified drug concentration over time inductively coupled plasma mass spectrometry blood serum, (including regions), target organs liver, kidney, colon. Our results indicate has a strong safety profile shows high (