Comparative study on two kinds of brain-targeted liposomes co-modified by RVGP and R9 in different ways

With the global aging population and rising tumor incidence, central nervous system degenerative diseases and brain tumors have emerged as critical threats to human health. Leveraging the biological properties of the blood-brain barrier (BBB), the development of dual-mediated brain-targeted liposome...

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Bibliographic Details
Main Authors: Yu Hei, Xin Wang, Yang Chen, Zi Mei, Xuebing Yang, ZhaoShuai Ji, Ying Xie
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:International Journal of Pharmaceutics: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590156725000374
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Summary:With the global aging population and rising tumor incidence, central nervous system degenerative diseases and brain tumors have emerged as critical threats to human health. Leveraging the biological properties of the blood-brain barrier (BBB), the development of dual-mediated brain-targeted liposomes via receptor-mediated and adsorption-mediated mechanisms holds promise for overcoming limitations such as lysosomal entrapment and saturation in single-receptor systems, thereby enabling efficient brain drug delivery. In this study, we constructed two types of dual-mediated liposomes using the BBB-specific ligand RVGP and cell-penetrating peptide R9 through distinct strategies: the monoligand liposome RVGPR9-SSL (incorporating both ligands as a single conjugate) and the biligand liposome RVGP-R9-SSL (displaying ligands as separate moieties). An in-depth comparative analysis of their BBB permeability and transport mechanisms was performed. Results demonstrate that RVGPR9-SSL circumvents lysosomal degradation via an endoplasmic reticulum-mediated transport pathway, exhibiting superior brain-targeted delivery efficiency and an excellent safety profile. These findings establish RVGPR9-SSL as an efficient brain-targeted drug delivery system with broad therapeutic potential for central nervous system disorders. Moreover, this study provides critical insights for the rational design of next-generation dual-mediated brain-targeted liposomal systems.
ISSN:2590-1567