Publication

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

Gholizadeh, S., Visweswaran, G. R. R., Storm, G., Hennink, W. E., Kamps, J. A. A. M. & Kok, R. J. 15-Sep-2018 In : International Journal of Pharmaceutics. 548, 2, p. 759-770 12 p.

Research output: Contribution to journalArticle

  • Shima Gholizadeh
  • Ganesh Ram R. Visweswaran
  • Gert Storm
  • Wim E. Hennink
  • Jan A. A. M. Kamps
  • Robbert J. Kok

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-alpha (TNF-alpha) 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-alpha 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.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume548
Issue number2
StatePublished - 15-Sep-2018
Event10th European Workshop on Particulate Systems (EWPS) - Copenhagen, Denmark
Duration: 19-Jan-201720-Jan-2017

Event

10th European Workshop on Particulate Systems (EWPS)

19/01/201720/01/2017

Copenhagen, Denmark

Event: Conference

    Keywords

  • Immunoliposomes, Rapamycin, Targeted delivery, Endothelial cells, PROTEIN-KINASE B, MAMMALIAN TARGET, TNF-ALPHA, EXPERIMENTAL ARTHRITIS, RHEUMATOID-ARTHRITIS, ACTIN CYTOSKELETON, LIPID-BILAYERS, CANCER-THERAPY, IN-VITRO, MTOR

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