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Introduction: The efficiency of brain therapeutics is greatly hindered by the blood-brain barrier (BBB). BBB's protective function, selective permeability, and dynamic functionality maintain the harmony between the brain and peripheral region. Thus, the design of any novel drug carrier system requires the complete study and investigation of BBB permeability, efflux transport, and the effect of associated cellular and non-vascular unit trafficking on BBB penetrability. The in vitro BBB models offer a most promising, and reliable mode of initial investigation of BBB permeability and associated factors as strong evidence for further preclinical and clinical investigation.
Area Covered: This review work covers the structure and functions of BBB components and different types of in vitro BBB models along with factors affecting BBB model development and model selection criteria.
Expert Opinion: In vivo models assume to reciprocate the physiological environment to the maximum extent. However, the interspecies variability, NVUs trafficking, dynamic behavior of BBB, etc., lead to non-reproducible results. The in vitro models are comparatively less complex, and flexible, as per the study design, could generate substantial evidence and help identify suitable in vivo animal model selection.
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http://dx.doi.org/10.1080/17425247.2023.2295940 | DOI Listing |
Mol Biol Rep
September 2025
Department of Pharmacology, Govt. College of Pharmacy, Rohru, Shimla, Himachal Pradesh, 171207, India.
Alzheimer's disease (AD) is the most common, complex, and untreatable form of dementia which is characterized by severe cognitive, motor, neuropsychiatric, and behavioural impairments. These symptoms severely reduce the quality of life for patients and impose a significant burden on caregivers. The existing therapies offer only symptomatic relief without addressing the underlying silent pathological progression.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Gamal Abdel Nasser, 11835, New Cairo, Egypt.
Licochalcone A (LCA), a natural flavonoid with potent anti-inflammatory properties, has shown promise as a neuroprotective agent. However, its ability to cross the blood-brain barrier (BBB) and exert central effects remains underexplored. In this study, we demonstrate for the first time that LCA enhances cognitive function in a lipopolysaccharide (LPS)-induced neuroinflammatory mouse model and effectively penetrates the BBB.
View Article and Find Full Text PDFAdv Pharm Bull
July 2025
R.C. Patel Institute of Pharmaceutical Education and Research, Industrial Pharmacy Laboratory, Department of Pharmaceutics, Shirpur 425405, Maharashtra, India.
Treatment of glioblastoma multiforme (GBM) has been a great challenge before medical fraternity since last century owing to a median survival of less than 15 months, despite of intensive therapy. Neurosurgeries, intense chemotherapy, advanced radiotherapy, and targeted therapies have bought some extension to the life of GBM patients. Combination and targeted therapies could bring a concrete approach to tackle the complexities of GBM treatment.
View Article and Find Full Text PDFAdv Mater
September 2025
State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
Delivering therapeutics across the blood-brain barrier (BBB) remains a major challenge in ischemic stroke therapy. Ischemic stroke induces upregulation of various inflammatory membrane receptors on brain endothelial cells, offering potential entry points for receptor-mediated transcytosis. This study proposes a universal targeting strategy by employing inflammatory pathway antagonists as targeting ligands, which broadens the spectrum of available ligands beyond traditional receptor-binding molecules.
View Article and Find Full Text PDFJ Med Chem
September 2025
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Proteasome inhibitors are effective in treating hematologic cancers but have limited utility in brain tumors due to poor blood-brain barrier (BBB) penetration and metabolic instability. In this study, we developed novel macrocyclic peptide epoxyketone inhibitors with improved drug-like properties. Compounds were screened for cytotoxicity against brain cancer cell lines, permeability (PAMPA-BBB and Caco-2), and metabolic stability.
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