Authors:

Lev Titov

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About Paper:

Sepsis, often followed by Septic shock, is a life-threatening condition caused by Gram-negative bacterial infections. Gram-negative infection introduces pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) into the system. Circulating LPS induces excessive release of pro-inflammatory cytokines, chemokines, and reactive oxygen species, causing hyperinflammation, immunosuppression, disseminated intravascular coagulation, and multiple organ failures. Polymyxin B, a cationic antimicrobial peptide, can adsorb to and inactivate LPS. However, the systemic use of Polymyxin B is challenged due to its dose-limiting toxicity. To mitigate the toxicity of Polymyxin B while maintaining its therapeutic efficacy, we have developed a nanoparticle consisting of albumin, tannic acid, and iron, as a carrier of Polymyxin B. The Polymyxin B-loaded nanoparticles (called TAPout) inactivated LPS endotoxicity, which is similar to unformulated PMB and a previously reported nanoparticle containing chitosan, in vitro and in vivo. TAPout particles demonstrated full survival from pre-induced sepsis by LPS injection upon intravenous injection, indicating that the TAPout particles are preventing LPS-induced sepsis, demonstrating protection against LPS- induced endotoxemia. Keywords: Gram-Negative Sepsis; Polymyxin B; Nanoparticle; Albumin

Source:

Purdue University / 2024

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Co-authors:

Lev Titov