ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Veterinary Pharmacology and Toxicology
PLGA nanoparticles loaded with recombinant antimicrobial protein PIP significantly improves the survival state and pathological damage caused by ETEC O8-induced sepsis in mice
Provisionally accepted
Xian Li1,2Jianjie Li3
Ying Zhang2Chunjiang Wang3Menglong Yue2Congshang Lei2
Miao Yin1,2
Xiwen Chen1*
Xuefeng Qi2*- 1Mianyang Normal University, Mianyang, China
- 2Northwest A&F University, Xianyang, China
- 3Hebei Veyong Pharmaceutical Co.,Ltd, Hebei, China
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Peptide-based antimicrobial drugs have the potential to be alternatives to antibiotics due to their broad-spectrum bactericidal properties and unique mechanism of membrane disruption in pathogens. In our previous research, the recombinant antimicrobial protein PIL22-PBD-2 (PIP) has been shown to inhibit pathogens and repair intestinal cell damage in vitro. However, the potential for treating bacterial infections within the body has not been evaluated. Here, we have developed an oral drug delivery nano-platform composed of PIP and poly (lactic-co-glycolic) acid (PLGA), and investigated its therapeutic effect on sepsis mice infected with Enterotoxigenic Escherichia coli O8 (ETEC O8). Our results indicate that PLGA-PIP has been successfully developed by using the double emulsion volatilization method and exhibited excellent resistance to destruction by trypsin. The safety test shows that PLGA-PIP has good biocompatibility in vivo. The results of sepsis treatment in mice show that compared with the ETEC O8 group, PLGA-PIP (300 mg/kg) can alleviate weight loss and clinical symptoms (p < 0.05), reduce serum biochemical index levels, lower organ indexes (p < 0.05), and decrease the load of ETEC O8 in feces, liver, spleen, and kidneys (p < 0.01). Additionally, compared with the ETEC O8 group, the PLGA-PIP group showed reduced severity of organ pathological damage, increased height of duodenal villi and VH/CD values (p < 0.05), upregulated expression levels of duodenal intercellular junction proteins ZO-1 and E-cadherin (p < 0.01), as well as endogenous antimicrobial Cryptdin-1 and regenerating islet derived protein 3 Gamma (Reg3γ) (p < 0.01), and decreased the expression levels of inflammatory factors IL-6, IL-1β, and TNF-α (p < 0.01). This study suggests that PLGA-PIP provides effective treatment for sepsis in mice and has the potential to become an alternative to antibiotic.
Keywords: antibiotic alternatives, ETEC O8, PLGA-PIP nanoparticles, Sepsis, treatment effect
Received: 19 Oct 2025; Accepted: 13 Jan 2026.
Copyright: © 2026 Li, Li, Zhang, Wang, Yue, Lei, Yin, Chen and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiwen Chen
Xuefeng Qi
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