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Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Enhanced Brain Targeting Delivery of Salvianic Acid Using Borneol as a Promoter of Blood/Brain Transport and Regulator of P-gp

Author(s): Ailing Hui*, Zheng Zhang, Jinghe Wang, Li Yang, Shaohuan Deng, Wencheng Zhang, An Zhou and Zeyu Wu

Volume 21, Issue 5, 2024

Published on: 08 February, 2023

Page: [726 - 733] Pages: 8

DOI: 10.2174/1567201820666230119120314

Price: $65


Background: Borneol can enhance the blood-brain barrier (BBB) permeability of some drugs and suppress the efflux transport of P-glycoprotein (P-gp), which will contribute to the brain delivery of salvianic acid A (SAA).

Objective: The study aimed to develop an approach to improve the brain targeting delivery of SAA with the aid of borneol.

Materials and Methods: “Borneol” was involved in SAA via esterified prodrug SAA borneol ester (SBE) and combined administration (SAA-borneol, SAA-B). Subsequently, the blood-brain transport of SAA through brain/blood distribution and P-gp regulation via expression and function assay were investigated in rats.

Results: The SBE and SAA-B-treated group received a three-fold brain concentration and longer t1/2 and retention period of active SAA than that of SAA alone (20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min). In addition, blood to brain transport of active SAA in SBE was altered in comparison to that of SAA-B, ultimately resulting in a better drug targeting index (9.93 vs. 3.63). Further studies revealed that SBE-induced downregulation of P-gp expression occurred at the later stage of administration (60 min, P < 0.01), but SBE always showed a more powerful drug transport activity across BBB represented by Kp value of rhodamine 123 than SAA-B (30, 60 min, P < 0.05).

Conclusion: The comparative results indicate that SBE exhibits prominent efficiency on SAA's targeting delivery through improved blood/brain metabolic properties and sustained inhibitory effect of “borneol” on P-gp efflux. Therefore, prodrug modification can be applied as a more effective approach for brain delivery of SAA.

Keywords: Borneol, blood-brain barrier, P-glycoprotein (P-gp), salvianic acid A (SAA), brain targeting delivery, prodrug, combined administration, salvianic acid a borneol ester.

Graphical Abstract
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