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Updated: Oct 25, 2025
Native Cell Membrane Nanoparticles System for Membrane Protein-Protein Interaction Analysis
Published on: July 16, 2020
Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis
Simseok A Yuk1, Hyungjun Kim1,2, Nader S Abutaleb3,4
1Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Abstract:
Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.
Insights
A novel nanoparticle system, D-TZP, effectively treats Gram-negative sepsis by reducing Polymyxin B toxicity while maintaining its antibacterial and endotoxin-inactivating properties. This breakthrough offers a safer systemic intervention for sepsis patients.
Area of Science:
- Nanomedicine
- Pharmacology
- Infectious Diseases
Background:
- Systemic treatment of Gram-negative sepsis is challenging.
- Polymyxin B (PMB) shows promise for sepsis due to its endotoxin affinity and antibacterial activity, but dose-limiting toxicity restricts its use.
- Developing safer delivery systems for PMB is crucial for effective sepsis therapy.
Purpose of the Study:
- To develop and evaluate a nanoparticulate system (D-TZP) for safe systemic delivery of Polymyxin B.
- To assess D-TZP's ability to reduce PMB-associated toxicity to mammalian cells while preserving its therapeutic efficacy against Gram-negative bacteria and endotoxins.
- To determine D-TZP's effectiveness in animal models of endotoxemia and sepsis.
Main Methods:
- D-TZP was formulated as an iron-complexed tannic acid nanocapsule with a vitamin D core, coated with PMB and a chitosan derivative.
- In vitro studies assessed D-TZP's membrane toxicity, endotoxin inactivation, and antibacterial activity against Gram-negative bacteria.
- In vivo studies evaluated D-TZP's efficacy in protecting animals from pre-established endotoxemia and polymicrobial sepsis after intravenous injection.
Main Results:
- D-TZP significantly attenuated the membrane toxicity of PMB.
- D-TZP retained the endotoxin-inactivating and Gram-negative antibacterial activities of PMB.
- Intravenous administration of D-TZP protected animals from endotoxemia and sepsis without exhibiting PMB-inherent toxicities.
Conclusions:
- D-TZP represents a safe and effective nanoparticulate system for the systemic delivery of Polymyxin B.
- This novel system overcomes the toxicity limitations of PMB, offering a promising therapeutic strategy for Gram-negative sepsis.
- D-TZP supports the potential for enhanced systemic intervention in sepsis management.
