E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells

Int J Pharm. 2018 Sep 15;548(2):759-770. doi: 10.1016/j.ijpharm.2017.10.027. Epub 2017 Oct 13.


Activated endothelial cells play a pivotal role in the pathology of inflammatory disorders and thus present a target for therapeutic intervention by drugs that intervene in inflammatory signaling cascades, such as rapamycin (mammalian target of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin immunoliposomes for targeted delivery to E-selectin over-expressing tumor necrosis factor-α (TNF-α) activated endothelial cells. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3.;hosphocholine (DPPC), Cholesterol, and 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleimide (DSPE-PEG-Mal) were loaded with rapamycin via lipid film hydration, after which they were further functionalized by coupling N-succinimidyl-S-acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these immunoliposomes bound specifically to TNF-α activated endothelial cells. Upon internalization, rapamycin loaded immunoliposomes inhibited proliferation and migration of endothelial cells, as well as expression of inflammatory mediators. Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically inhibit inflammatory responses in inflamed endothelial cells.

Keywords: Endothelial cells; Immunoliposomes; Rapamycin; Targeted delivery.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / immunology
  • Anti-Bacterial Agents / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • E-Selectin / administration & dosage*
  • E-Selectin / immunology
  • E-Selectin / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Liposomes
  • Mice
  • Sirolimus / administration & dosage*
  • Sirolimus / immunology
  • Sirolimus / metabolism


  • Anti-Bacterial Agents
  • E-Selectin
  • Liposomes
  • Sirolimus