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Additionally, chemical modification strategies (e.g., methylation, etherification, conjugation of BBB-targeting groups) or targeted synthesis based on BBB penetration principles can optimise physicochemical properties (e.g., reducing water solubility, enhancing lipophilicity to match the BBB’s lipid bilayer characteristics) or evade recognition by BBB efflux transporters, thereby significantly improving target drug penetration efficiency (Narsinh et al., 2024)

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Nakazawa D, Masuda S, Tomaru U, Ishizu A