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Development and pre-clinical use of 3D all-human in vitro models of the blood brain barrier under static and dynamic/flow conditions and apprpriate serum, oxygen and basal lamina conditions.

Existing collaborations relevant to drug delivery

Many at National & International levels.

Publications relevant to drug delivery

Prospero Civita, Diana M. Leite and Geoffrey J. Pilkington. Pre-clinical drug testing in 2D and 3D human in vitro models incorporating non-neoplastic astrocytes; tunneling nanotubules and mitochondrial transfer modulate cell behaviour and therapeutic response in GBM. International Journal of Molecular Sciences 2019, 20, 6017; doi:10.3390/ijms20236017 (29th November 2019)

Synnøve Nymark Aasen, Heidi Espedal, Christopher Florian Holte, Olivier Keunen, Tine Veronika Karlsen, Olav Tenstad, Zaynah Maherally, Hrvoje Miletic, Tuyen Thi Van Hoang, Anne Vaag Eikeland, Habib Baghirov, Dag Erlend Olberg, Geoffrey J. Pilkington, Gobinda Sarkar, Robert Jenkins, Terje Sundstrøm, Rolf Bjerkvig and Frits Thorsen. Improved drug delivery to brain metastases by peptide-mediated permeabilization of the blood-brain barrier Molecular Cancer Therapeutics DOI: 10.1158/1535-7163.MCT-19-0160 August 29th 2019.

Diana M. Leite, Barbara Zvar Baskovic, Prospero Civita, Catia Neto, Mark Gumbleton and Geoffrey J. Pilkington. A Human Co-culture Cell Model Incorporating Microglia Supports Glioblastoma Growth and Migration, and Confers Resistance to Cytotoxics. FASEB Journal First published: 05 December 2019 https://doi.org/10.1096/fj.201901858RR

Samah A. Jassam, Zaynah Maherally, Keyoumars Ashkan, Geoffrey J. Pilkington, Helen L Fillmore. Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood-brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis. Journal of Neuro-oncology doi.org/10.1007/s11060-019-03188-x (2019)

Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, Hatherell KE, Pilkington GJ. Real-time acquisition of trans-endothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood–brain barrier model exemplifies tight-junction integrity. The FASEB Journal. 2018 Jan 1;32(1):168-82.

Jassam SA, Maherally Z, Smith JR, Ashkan K, Roncaroli F, Fillmore HL, Pilkington GJ. CD15s/CD62E interaction mediates the adhesion of non-small cell lung cancer cells on brain endothelial cells: implications for cerebral metastasis. International Journal of Molecular Sciences. 2017 Jul 10;18(7):1474.

Toman P, Lien CF, Ahmad Z, Dietrich S, Smith JR, An Q, Molnár É, Pilkington GJ, et al. Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: Preparation and in vitro investigation. Acta biomaterialia. 2015 Sep;23: 250-62. PubMed PMID: 25983313.

Jassam SA, Maherally Z, Smith JR, Ashkan K, Roncaroli F, Fillmore HL, Pilkington GJ. TNF-alpha enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis. Neuro-oncology. 2015 Oct 15. PubMed PMID: 26472821. Neuro Oncol. 2016 May;18(5):679-90. doi: 10.1093/neuonc/nov248. Epub 2015 Oct 15.

Leite DM, Barbu E, Pilkington GJ, Lalatsa A. Peptide Self-Assemblies for Drug Delivery. Current topics in medicinal chemistry. 2015;15(22):2277-89. PubMed PMID: 26043734.

Lien CF, Molnar E, Toman P, Tsibouklis J, Pilkington GJ, Gorecki DC, et al. In vitro assessment of alkylglyceryl-functionalized chitosan nanoparticles as permeating vectors for the blood-brain barrier. Biomacromolecules. 2012 Apr 9;13(4):1067-73. PubMed PMID: 22409486.