Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line.
Abstract
The targeting potential of OX-26-decorated immunoliposomes was investigated, using the human brain endothelial cell line hCMEC/D3 as a model of the blood-brain barrier (BBB). Immuno-nanoliposomes were prepared by the biotin/streptavidin ligation strategy, and their uptake by hCMEC/D3 cells and permeability through cell monolayers was studied. In order to elucidate the mechanisms of uptake, pH-sensitive fluorescence signal of HPTS was used, while transport was measured using double labeled immunoliposomes (with aqueous and lipid membrane fluorescent tags). PEGylated and non-specific-IgG-decorated liposomes were studied under identical conditions, as controls. CHO-K1 cells (which do not overexpress the transferrin receptor) were studied in some cases for comparative purposes. Experimental results reveal that hCMEC/D3 cells are good models for in vitro screening of BBB-targeting nanoparticulate drug delivery systems. Uptake and transcytosis of immunoliposome-associated dyes by cell monolayers was substantially higher compared to those of control liposomes. HPTS-entrapping OX-26-immunoliposome uptake indicated lysosomal localization and receptor-mediated mechanism. The ratio of aqueous/lipid label transport is affected by pre-incubation with antibody, or use of high lipid doses, suggesting that vesicles are transported intact after lysosome saturation. Co-decoration with a second ligand slightly decreases OX-26-decorated vesicle uptake, but not transcytosis, proving that the biotin-streptavidin technique can be applied for the generation of dual-targeting nanoliposomes.
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Physiochemical properties of drug-loaded nanocarriers such as hydrophilicity, surface charge, and targeting ligands determine adsorption on brain capillary endothelial cells.
“The physiochemical properties of drug loaded nanocarrier like hydrophilicity, surface charge and targeting ligands of nano carrier is the deciding factor for the adsorption on the brain capillary endothelial cells”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Markoutsa et al., 2011
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The hCMEC/D3 cell line as a model of the human blood brain barrier
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- Authors
- Markoutsa, E., Pampalakis, G., Niarakis, A., Romero, I. A., Weksler, B., Couraud, P.-O., & Antimisiaris, S. G.
- Affiliations
- University of Patras (GR)
- The Open University (GB)
- Cornell University (US)
- Inserm (FR)
- Corresponding author
- Antimisiaris, Sophia G.
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 77
- Issue
- 2
- Pages
- 265-274
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W2035669214
- Cited by
- 122
- References
- 44
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 3 · 2019: 8 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 7 · 2014: 17 · 2013: 12 · 2012: 5
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Open Research Online - ORO (The Open University) (acceptedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- immunoliposomes, blood-brain barrier targeting, hCMEC/D3 cells, transferrin receptor, receptor-mediated uptake, transcytosis, lysosomal uptake, PEGylated liposomes, HPTS, brain drug delivery
- MeSH terms
- Animals, Antibodies, Monoclonal, Biological Transport, Blood-Brain Barrier, Cell Line, Cell Survival, Cells, Cultured, Humans, Immunoglobulin G, Liposomes, Particle Size, Permeability, Receptors, Transferrin, Transferrin, Endothelial Cells, Mice, Nanoparticles, Chemical Phenomena, Transcytosis
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