Journal
JOURNAL OF CONTROLLED RELEASE
Volume 321, Issue -, Pages 463-474Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2020.02.030
Keywords
Lung infection and sepsis; PLGA nanoparticles; Co-delivery drugs; gamma 3 peptide
Funding
- National Natural Science Foundation of China [21604072, 51673171, 81773096]
- National Key Research and Development Program of China [2016YFE0132700]
- Key Research and Development Program of Zhejiang Province [2018C03085]
- Public Welfare Technology Research Project of Zhejiang Province [LGD19C040006]
- General Research Project of the Zhejiang Provincial Education Department [Y201840044]
- Zhejiang Province Department of Laboratory Animal Science and Technology Plan Projects [2018C37115]
- Fundamental Research Funds for the Central Universities of China [2019XZZX004-07]
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Sepsis is a complex disorder with very high morbidity and mortality; it can occur when an immune disorder triggers an invasion of pathogens in the host. Although many potential anti-infective and immunosuppressive treatments have been reported, we still do not have effective means of treating sepsis in clinic. The aim of this study is to develop a nanomaterial system that targets the site of inflammation and carries a combination of multiple drugs to better treat sepsis and alleviate its symptoms. We selected poly(lactide-co-glycolide acid) (PLGA) with good biocompatibility and degradability to prepare the nanoparticles (NPs) loaded with broad-spectrum antibiotic Sparfloxacin (SFX) and anti-inflammatory immunosuppressant Tacrolimus (TAC) by an emulsion-solvent evaporation method. The targeting ability of the NPs toward inflammatory sites is endowed by grafting of the gamma 3 peptide (NNQKIVNLKEKVAQLEA) that can specifically bind to the intercellular adhesion molecule-1 (ICAM-1), which is highly expressed on the surface of inflammatory endothelial cells. The drug loaded gamma 3-PLGA NPs have excellent cytocompatibility, low hemolysis ratio, and systemic toxicity. The drug loaded gamma 3-PLGA NPs also have excellent antibacterial property to both Gram-positive and Gram-negative bacteria and can effectively reduce the inflammation and immune response in acute lung infection mice. This study provides a simple and robust nanoplatform to treat lung infection induced sepsis, which may pave a way to design multifunctional nanomedicine for clinical translation.
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