Characterization of pathological blood-brain barrier crossing BSc3094 nanopreparations and evaluation of their targeting properties
10.16438/j.0513-4870.2024-0750
- VernacularTitle:病理血脑屏障穿越BSc3094纳米制剂的制备表征及其靶向性评价
- Author:
Hang LUO
1
;
Yue LÜ
2
;
Hui-le GAO
2
;
Jing-yuan XIONG
1
Author Information
1. West China School of Public Health/the Fourth Hospital of West China, Sichuan University, Chengdu
2. West China College of Pharmacy, Sichuan University, Chengdu
- Publication Type:Research Article
- Keywords:
Alzheimer′s disease;
Tau protein;
nanoparticle;
BSc3094;
blood-brain barrier
- From:
Acta Pharmaceutica Sinica
2024;59(12):3388-3393
- CountryChina
- Language:Chinese
-
Abstract:
Intracellular neurofibrillary tangles resulting from abnormal hyperphosphorylation of Tau protein constitute one of the principal pathological markers of Alzheimer′s disease. Existing studies have indicated that BSc3094 is an efficacious inhibitor of Tau protein aggregation, capable of binding to Tau protein, inhibiting Tau protein phosphorylation, and enhancing cell viability concurrently, holding significant potential in treating Alzheimer′s disease. Nevertheless, due to the presence of the blood-brain barrier, it is challenging for drugs to penetrate the brain and exert their effects, and whether BSc3094 can treat Alzheimer′s disease by inhibiting Tau protein aggregation has not been profoundly investigated. Hence, in this study, small-sized (PLGA) nanoparticles were fabricated through the stirring method. BSc3094 was loaded into the nanoparticles (PLGA@BSc). To further enhance the brain entry efficiency of PLGA nanoparticles, a pathological BBB-targeting peptide was modified on the surface to obtain PLGA@BSc@K. In this study, the stability, cytotoxicity, and pathological targeting of the nanosystem were characterized. The particle size of the nanosystem was about 90 nm, which was negatively charged. The results demonstrated that the particle size of the nanoparticles did not fluctuate conspicuously within 168 h, and the stability was favorable. PLGA and BSc3094 had no notable impact on cell viability and displayed low cytotoxicity. At 1 and 4 h, it was observed that the uptake of targeted modified nanoparticles by cells in pathological states augmented, suggesting that PLGA@BSc@K had an excellent pathological blood-brain barrier targeting effect. This study provides a novel concept for the targeting of BSc3094 nanoparticles in the brain and the treatment of Alzheimer′s disease.
