Publication

PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium

Gholizadeh, S., Kamps, J. A. A. M., Hennink, W. E. & Kok, R. J., 15-Sep-2018, In : International Journal of Pharmaceutics. 548, 2, p. 747-758 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Gholizadeh, S., Kamps, J. A. A. M., Hennink, W. E., & Kok, R. J. (2018). PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium. International Journal of Pharmaceutics, 548(2), 747-758. https://doi.org/10.1016/j.ijpharm.2017.10.032

Author

Gholizadeh, Shima ; Kamps, Jan A A M ; Hennink, Wim E ; Kok, Robbert J. / PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium. In: International Journal of Pharmaceutics. 2018 ; Vol. 548, No. 2. pp. 747-758.

Harvard

Gholizadeh, S, Kamps, JAAM, Hennink, WE & Kok, RJ 2018, 'PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium', International Journal of Pharmaceutics, vol. 548, no. 2, pp. 747-758. https://doi.org/10.1016/j.ijpharm.2017.10.032

Standard

PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium. / Gholizadeh, Shima; Kamps, Jan A A M; Hennink, Wim E; Kok, Robbert J.

In: International Journal of Pharmaceutics, Vol. 548, No. 2, 15.09.2018, p. 747-758.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Gholizadeh S, Kamps JAAM, Hennink WE, Kok RJ. PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium. International Journal of Pharmaceutics. 2018 Sep 15;548(2):747-758. https://doi.org/10.1016/j.ijpharm.2017.10.032


BibTeX

@article{6079aec480a048799d176982daab3374,
title = "PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium",
abstract = "Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual mTOR/PI3 K inhibitor that is of potential interest in the treatment of inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric nanoparticles composed of a blend of poly(D, L-lactide-co-glycolide) (PLGA) and poly(D, L-lactide-coglycolide)- poly(ethylene glycol)-2000 (PLGA-PEG). The nanoparticles were prepared by an oil/water emulsion solvent evaporation method, and were subsequently characterized for yield, encapsulation efficiency, morphology, particle size, drug-polymer interaction and in vitro drug release profiles. A targeted formulation was developed by conjugation of a S-acetyl-thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The particle size distribution showed a range from 250 to 360 nm with a high (> 75{\%}) BEZ encapsulation efficiency. Approximately 35{\%} of the loaded BEZ was released within 10 days at 37 degrees C in a medium containing 5{\%} bovine serum albumin (BSA). Evaluation of efficacy of anti E-selectin decorated BEZ-loaded nanoparticles was carried out in tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Confocal microscopy analysis showed that cellular uptake of the targeted nanoparticles and subsequent internalization. Cell functional assays, including migration assay and phosphowestern blot analysis of the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated endothelial cells as compared to the non-targeted BEZloaded nanoparticles. In conclusion, E-selectin targeted nanoparticles have a high potential in delivering the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are an interesting nanomedicine for anti-inflammatory therapy.",
keywords = "Targeted delivery, PLGA, NVP-BEZ235, Nanoparticles, Inflammation, PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET, IN-VITRO DEGRADATION, SAINT-O-SOMES, DRUG-DELIVERY, CELL-MIGRATION, PI3K/AKT/MTOR PATHWAY, RAPAMYCIN INHIBITOR, SELECTIVE DELIVERY, CANCER",
author = "Shima Gholizadeh and Kamps, {Jan A A M} and Hennink, {Wim E} and Kok, {Robbert J}",
note = "Copyright {\circledC} 2017 The Authors. Published by Elsevier B.V. All rights reserved.",
year = "2018",
month = "9",
day = "15",
doi = "10.1016/j.ijpharm.2017.10.032",
language = "English",
volume = "548",
pages = "747--758",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier Bedrijfsinformatie b.v.",
number = "2",

}

RIS

TY - JOUR

T1 - PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor dactolisib to inflamed endothelium

AU - Gholizadeh, Shima

AU - Kamps, Jan A A M

AU - Hennink, Wim E

AU - Kok, Robbert J

N1 - Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual mTOR/PI3 K inhibitor that is of potential interest in the treatment of inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric nanoparticles composed of a blend of poly(D, L-lactide-co-glycolide) (PLGA) and poly(D, L-lactide-coglycolide)- poly(ethylene glycol)-2000 (PLGA-PEG). The nanoparticles were prepared by an oil/water emulsion solvent evaporation method, and were subsequently characterized for yield, encapsulation efficiency, morphology, particle size, drug-polymer interaction and in vitro drug release profiles. A targeted formulation was developed by conjugation of a S-acetyl-thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The particle size distribution showed a range from 250 to 360 nm with a high (> 75%) BEZ encapsulation efficiency. Approximately 35% of the loaded BEZ was released within 10 days at 37 degrees C in a medium containing 5% bovine serum albumin (BSA). Evaluation of efficacy of anti E-selectin decorated BEZ-loaded nanoparticles was carried out in tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Confocal microscopy analysis showed that cellular uptake of the targeted nanoparticles and subsequent internalization. Cell functional assays, including migration assay and phosphowestern blot analysis of the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated endothelial cells as compared to the non-targeted BEZloaded nanoparticles. In conclusion, E-selectin targeted nanoparticles have a high potential in delivering the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are an interesting nanomedicine for anti-inflammatory therapy.

AB - Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual mTOR/PI3 K inhibitor that is of potential interest in the treatment of inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric nanoparticles composed of a blend of poly(D, L-lactide-co-glycolide) (PLGA) and poly(D, L-lactide-coglycolide)- poly(ethylene glycol)-2000 (PLGA-PEG). The nanoparticles were prepared by an oil/water emulsion solvent evaporation method, and were subsequently characterized for yield, encapsulation efficiency, morphology, particle size, drug-polymer interaction and in vitro drug release profiles. A targeted formulation was developed by conjugation of a S-acetyl-thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The particle size distribution showed a range from 250 to 360 nm with a high (> 75%) BEZ encapsulation efficiency. Approximately 35% of the loaded BEZ was released within 10 days at 37 degrees C in a medium containing 5% bovine serum albumin (BSA). Evaluation of efficacy of anti E-selectin decorated BEZ-loaded nanoparticles was carried out in tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Confocal microscopy analysis showed that cellular uptake of the targeted nanoparticles and subsequent internalization. Cell functional assays, including migration assay and phosphowestern blot analysis of the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated endothelial cells as compared to the non-targeted BEZloaded nanoparticles. In conclusion, E-selectin targeted nanoparticles have a high potential in delivering the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are an interesting nanomedicine for anti-inflammatory therapy.

KW - Targeted delivery

KW - PLGA

KW - NVP-BEZ235

KW - Nanoparticles

KW - Inflammation

KW - PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET

KW - IN-VITRO DEGRADATION

KW - SAINT-O-SOMES

KW - DRUG-DELIVERY

KW - CELL-MIGRATION

KW - PI3K/AKT/MTOR PATHWAY

KW - RAPAMYCIN INHIBITOR

KW - SELECTIVE DELIVERY

KW - CANCER

U2 - 10.1016/j.ijpharm.2017.10.032

DO - 10.1016/j.ijpharm.2017.10.032

M3 - Article

VL - 548

SP - 747

EP - 758

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 2

ER -

ID: 49892308