E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cellsGholizadeh, 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 journal › Article › Academic › peer-review
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.
|Number of pages||12|
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 15-Sep-2018|
|Event||10th European Workshop on Particulate Systems (EWPS) - Copenhagen, Denmark|
Duration: 19-Jan-2017 → 20-Jan-2017
10th European Workshop on Particulate Systems (EWPS)
19/01/2017 → 20/01/2017Copenhagen, Denmark
- 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