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

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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

26 Citaten (Scopus)
223 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)759-770
Aantal pagina's12
TijdschriftInternational Journal of Pharmaceutics
Volume548
Nummer van het tijdschrift2
DOI's
StatusPublished - 15-sep-2018
Evenement10th European Workshop on Particulate Systems (EWPS) - Copenhagen, Denmark
Duur: 19-jan-201720-jan-2017

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