Pluronic F127/lecithin PLGA nanoparticles as carriers of monocyte-targeted jakinibs: a potential therapeutic platform

Nanomedicine (Lond). 2025 Jan;20(1):9-22. doi: 10.1080/17435889.2024.2415877. Epub 2024 Oct 29.

Abstract

Aim: In this study, PLGA nanoparticles (PNPs) emulsified in Pluronic F127 (F127)/Lecithin (LEC) were designed to load Itacitinib (ITA), a selective JAK1 inhibitor, for targeting human monocytes.Materials & methods: The physicochemical characteristics of empty and ITA-loaded F127/LEC PNPs were analyzed. The binding and internalization of NPs in leukocytes were evaluated. The effect of NPs on monocyte activation and JAK1 inhibition was assessed.Results: F127/LEC PNPs were selectively bound and internalized by monocytes, sparing other leukocytes. ITA-F127/LEC PNPs significantly dampened monocyte activation. They also inhibited the monocyte's ability to promote T-cell proliferation and inhibited proinflammatory cytokine production.Conclusion: ITA-loaded F127/LEC PNPs showed potential for monocyte-targeted therapy, offering new avenues for disease treatment.

Keywords: JAK-STAT pathway; L-lactic-co-glycolic acid; jakinibs; monocytes; nanoparticles.

Plain language summary

[Box: see text].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Drug Carriers* / chemistry
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 1 / metabolism
  • Janus Kinase Inhibitors / chemistry
  • Janus Kinase Inhibitors / pharmacology
  • Janus Kinase Inhibitors / therapeutic use
  • Monocytes* / drug effects
  • Monocytes* / metabolism
  • Nanoparticles* / chemistry
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Poloxamer* / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry

Substances

  • Poloxamer
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Drug Carriers
  • Janus Kinase 1
  • Janus Kinase Inhibitors
  • JAK1 protein, human
  • Piperidines
  • Cytokines