UCLA researchers in the Department of Dentistry have found a novel use for nisin alone, and in formulations, for use in the treatment of Alzheimer’s disease, and multiple inflammation states such as brain inflammation, joint inflammation, oral inflammation, systemic inflammation, inflammatory bowel diseases, and non-alcoholic fatty liver disease (NAFLD).
BACKGROUND: Nisin is an antimicrobial bacteriocin produced by some Lactococcus and Streptococcus gram-positive bacteria species. The Food and Drug Administration (FDA) has determined that Nisin is a safe antimicrobial and has a low potential for developing bacterial resistance. Indeed, the research of Nisin for the use of clinical diseases is expansive and ranges from Alzheimer’s, inflammation to periodontal disease. A barrier into leveraging the properties of Nisin for the treatment of disease is finding the correct drug delivery system.
INNOVATION: Researchers led by Dr. Yvonne Kapila have incorporated Nisin into a nanoscale drug delivery system called Solid Lipid Nanoparticles (SLN). These SLNs are nanoparticles created from biocompatible lipids. They are highly stable for over a year while also having low transient toxicity in vivo. The Kapila group constructed Nisin-loaded SLN (SLN-Nisin) and has shown that SLN-Nisin amplifies antibacterial effects by 2 times, antimicrobial effects by 4 times and anticancer properties by 10 times when compared to free Nisin. In Alzheimer’s disease, data from the Kapila group indicate that Nisin can significantly reduce two proteins involved in Alzheimer’s disease progression, the amyloid plaques and Tau proteins, in the brains of mice with polymicrobial periodontal infections. The use of Nisin shows that there is a significant reduction in neuroinflammatory markers in the brain, indicating the use of Nisin for the treatment of Alzheimer’s. Nisin also reduces NAFLD parameters (fatty liver, liver inflammation, microbiome changes).
POTENTIAL APPLICATIONS:
- Delivery of Nisin at high efficacy rates.
- Nisin delivery can be used for multiple disease states including Alzheimer’s disease, periodontal disease, NAFLD
- Increase therapeutic efficacy of Nisin by using SLN-Nisin.
ADVANTAGES:
- Nisin can be delivered alone, or in formulations, vehicles, scaffolds, membranes, or in nano-sized delivery systems to treat multiple diseases and inflammation.
- Encapsulation of Nisin amplifies its antibacterial, antibiofilm, anticancer and antiinflammation properties.
DEVELOPMENT-TO-DATE: Researchers produced SLN-Nisin by the microemulsion extrusion technique, as well as created the Nisin formulation in vehicles and scaffolds. Data has determined that nisin significantly reduces neuroinflammatory markers in the mouse brain in vivo. Nisin also reduces periodontal disease inflammation and bone loss while promoting periodontal repair. Further, nisin reduces NAFLD parameters, including fatty liver, liver inflammation, and microbiome related changes.
Related Papers (from the inventors only)
Radaic, A., Malone, E., Kamarajan, P., Kapila, Y.L. Solid Lipid Nanoparticles Loaded with Nisin (SLN-Nisin) are More Effective Than Free Nisin as Antimicrobial, Antibiofilm, and Anticancer Agents. Journal of Biomedical Nanotechnology, 2022, 18(4):1227-1235.
Zhao C, Kuraji R, Ye C, Gao L, Radaic A, Kamarajan P, Taketani Y, Kapila YL. Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer's disease-like neuroinflammation triggered by periodontal disease. J Neuroinflammation. 2023 Oct 6;20(1):228. doi: 10.1186/s12974-023-02915-6. PMID: 37803465; PMCID: PMC10557354.
Gao L, Kuraji R, Zhang MJ, Martinez A, Radaic A, Kamarajan P, Le C, Zhan L, Ye C, Rangé H, Sailani MR, Kapila YL. Nisin probiotic prevents inflammatory bone loss while promoting reparative proliferation and a healthy microbiome. NPJ Biofilms Microbiomes. 2022 Jun 7;8(1):45. doi: 10.1038/s41522-022-00307-x. PMID: 35672331; PMCID: PMC9174264.
Kuraji R, Ye C, Zhao C, Gao L, Martinez A, Miyashita Y, Radaic A, Kamarajan P, Le C, Zhan L, Range H, Sunohara M, Numabe Y, Kapila YL. Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis. NPJ Biofilms Microbiomes. 2024 Jan 17;10(1):3. doi: 10.1038/s41522-024-00476-x. PMID: 38233485; PMCID: PMC10794237.