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Background <p>The blood–brain barrier (BBB) is a highly selective interface that protects the central nervous system but is vulnerable to chemical- and nanomaterial-induced dysfunction. Therefore, candidate nanocarriers should be evaluated not only for delivery performance, but also for cellular safety and barrier compatibility under physiologically relevant conditions.</p> Objectives <p>This study aimed to assess the cellular safety and barrier integrity associated with reassembled yeast vacuoles (ReV) compared with normal vacuoles (NorV) in an astrocyte-supported in vitro BBB model, while examining the mechanism by which these carriers influence daunorubicin (DNR) handling under barrier conditions.</p> Methods <p>In vitro BBB models were established using human brain microvascular endothelial cells (hCMEC/D3) as a monolayer and an astrocyte-supported Transwell co-culture model with human astrocytes seeded on the underside of the membrane. DNR was tested as a free drug or as loaded into ReV or NorV. Endothelial drug-associated fluorescence and transport-related signals were evaluated by fluorescence-based permeability testing and quantitative image analysis. Barrier integrity was monitored using transendothelial electrical resistance (TEER), and endothelial viability was assessed using an MTT assay.</p> Results <p>TEER remained stable following treatment, indicating no measurable barrier disruption under the tested conditions. MTT analysis showed no significant reduction in hCMEC/D3 viability within the tested dose range. In the monolayer BBB model, the intracellular DNR-associated fluorescence was comparable among the formulations. In contrast, in the astrocyte-supported BBB model, DNR@ReV produced a markedly higher endothelial DNR-associated fluorescence than free DNR or DNR@NorV.</p> Conclusion <p>Reassembled yeast vacuoles support DNR handling in an astrocyte-supported in vitro BBB model while maintaining endothelial viability and barrier integrity, providing a toxicology-relevant platform for screening yeast-derived nanocarriers for central nervous system-oriented. </p> Graphic abstract <p></p>

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Reassembled yeast vacuoles preserve endothelial viability and barrier integrity in an in vitro blood–brain barrier model

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Yoon-Young Hwang,
  • Cho-Im Oh,
  • Jin-Pyo Lee,
  • Su-Min Lee,
  • Dae-Young Park,
  • In-Hwan Oh,
  • Tae-rim Kim,
  • Ok Chan Jeong,
  • Ji-Young Ahn,
  • Yang-Hoon Kim,
  • Jiho Min

摘要

Background

The blood–brain barrier (BBB) is a highly selective interface that protects the central nervous system but is vulnerable to chemical- and nanomaterial-induced dysfunction. Therefore, candidate nanocarriers should be evaluated not only for delivery performance, but also for cellular safety and barrier compatibility under physiologically relevant conditions.

Objectives

This study aimed to assess the cellular safety and barrier integrity associated with reassembled yeast vacuoles (ReV) compared with normal vacuoles (NorV) in an astrocyte-supported in vitro BBB model, while examining the mechanism by which these carriers influence daunorubicin (DNR) handling under barrier conditions.

Methods

In vitro BBB models were established using human brain microvascular endothelial cells (hCMEC/D3) as a monolayer and an astrocyte-supported Transwell co-culture model with human astrocytes seeded on the underside of the membrane. DNR was tested as a free drug or as loaded into ReV or NorV. Endothelial drug-associated fluorescence and transport-related signals were evaluated by fluorescence-based permeability testing and quantitative image analysis. Barrier integrity was monitored using transendothelial electrical resistance (TEER), and endothelial viability was assessed using an MTT assay.

Results

TEER remained stable following treatment, indicating no measurable barrier disruption under the tested conditions. MTT analysis showed no significant reduction in hCMEC/D3 viability within the tested dose range. In the monolayer BBB model, the intracellular DNR-associated fluorescence was comparable among the formulations. In contrast, in the astrocyte-supported BBB model, DNR@ReV produced a markedly higher endothelial DNR-associated fluorescence than free DNR or DNR@NorV.

Conclusion

Reassembled yeast vacuoles support DNR handling in an astrocyte-supported in vitro BBB model while maintaining endothelial viability and barrier integrity, providing a toxicology-relevant platform for screening yeast-derived nanocarriers for central nervous system-oriented.

Graphic abstract