Present BBB layers | Cell types and origin | Drug delivery system | Therapeutic molecule | Results | Refs. |
---|---|---|---|---|---|
1 | hCMEC/D3 brain endothelial cell line | Lipid nanocapsules | Nonpsychotropic cannabinoids | This system outperformed G-Technology by sixfold crossing the in vitro BBB, a sustained drug delivery system to the brain currently in the last stage of clinical trials | [48] |
hIPSCs-derived brain endothelial cells | None | Immunoglobulin G | The antibody transport across the in vitro barrier is increased in the presence of amyloid-b and neuroinflammatory cytokines, proving to be a plausible therapy for Alzheimer’s disease | [49] | |
Primary human microvascular endothelial cells | None | Anti-amyloid-b monoclonal antibody | Anti-amyloid-b N-terminal antibodies allow clearance of amyloid-b across the BBB unlike Anti-amyloid-b C-terminal, due to a RAGE-based process | [50] | |
Bovine primary brain endothelial cells | Phage display-based HAIYPRH sequence containing peptides | None | MALDI-TOF allowed a more sensitive analysis of the BBB crossing peptides, allowing highly sensitive and low sample assays for peptide selection | [51] | |
hIPSC’s derived brain endothelial cells | None | Cyclosporine A | Evaluation of Cyclosporine A time and concentration dependent toxicity using a simple in vitro BBB model | [52] | |
hIPSC’s derived brain endothelial cells | None | Mannitol | The miniaturized in vitro model of BBB allows the visualization and characterization of the hyperosmotic permeability enhancement caused by mannitol dosages | [53] | |
hCMEC/D3 brain endothelial cell line | Recombinant human apoferritin nanoparticles | Anti-CTX and anti- TZ monoclonal antibodies | Using a glioblastoma cell line and a well plate insert BBB model, ferritin-based nanocarriers of monoclonal antibodies show BBB crossing capacity and posterior glioblastoma targeting | [54] | |
hCMEC/D3 brain endothelial cell line | Spheric and rod-shaped polystyrene particles | None | Rod-shaped particles overcome the BBB more easily than spherical particles of the same material | [41] | |
2 | Primary rat endothelial cells and astrocytes | Phage display derived peptides | None | The two selected peptides show particularly high BBB permeability as compared to control ones with 3.3 × 10−7 cm/s for GLHTSATNLYLH and 1.5 × 10−6 cm/s for VAARTGEIYVPW | [41] |
GLHTSATNLYLH and VAARTGEIYVPW for primary rat endothelial cells | |||||
Human CD34 + endothelial cells derived from hematopoietic stem cells | None | Methotrexate Levofloxacin Indomethacin Atenolol Diazepam Metoprolol Lamotrigine Verapamil Bupropion | The blood/cerebrospinal fluid (CSF) ratio for each of the used drugs matched the values acquired for this ratio in human patients with a correlation factor R2 = 0.88 | [55] | |
Murine immortalized endothelial cells and murine astrocytes | Transferrin and cell penetrating peptide PFVYLI modified liposomes | Doxorubicin and erlotinib | Dually modified liposomes showed significantly higher BBB crossing ability and glioblastoma cells’ death than controls | [56] | |
3 | hIPSCs derived brain microvascular endothelial cells and primary brain pericytes and astrocytes | 100–400 nm fluorescent polystyrene and 100 nm rhodamine-labeled polyurethane nanoparticles | None | The BBB vascularized microfluidic model allows rapid nanoparticle testing, concluding that both the commercial polystyrene and the custom-made polyurethane nanoparticles have similar BBB permeability | [57] |
hIPSCs derived brain microvascular endothelial cells and primary brain pericytes and astrocytes | None | Digoxin Colchicine Quinidine Vinblastine Glibenclaide Caffeinem Bupropion Gabapentin Lamotrigine Tacrine Thioridazine Topiramate Verapamil | Higher correlation of in vitro human BBB model crossing with human in vivo models of standard drugs than rat BBB and Caco-2 models | [58] | |
Immortalized human brain endothelial, brain pericytes and astrocytes | None | Propranolol Pyrilamine Memantine Diphenhydramine Sodium fluorescein Lucifer yellow | Immortalized BBB recreated the in vivo permeation profile of BBB permeable and non-permeable drugs | [59] |