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<p>Intranasal drug delivery via nanocarriers has long been a research focus for enhancing drug concentration in the brain. However, the strategy of exploiting blood–brain barrier (BBB) alterations in atherosclerotic mouse models to enhance nanoparticle-mediated delivery of bromocriptine to the hypothalamus for the treatment of prolactinomas with hyperprolactinemia has not yet been reported. This study reveals that in patients with prolactinomas complicated by arteriosclerosis, bromocriptine therapy more effectively attenuates postoperative elevations in prolactin levels. In a mouse model, liposome-encapsulated bromocriptine efficiently traversed the nasal mucosa and entered the intracranial space. Compared with normal mice, bromocriptine-loaded liposomes delivered higher bromocriptine concentrations to the hypothalamus. Single-cell RNA sequencing revealed a significant upregulation of organic anion-transporting polypeptide 1a4 (Oatp1a4) expression in the brain endothelial cells of atherosclerotic mice. Importantly, bromocriptine-loaded liposomes more effectively reduced prolactin levels in a mouse model of prolactinoma with concurrent atherosclerosis. This study provides a theoretical foundation for the precision treatment of prolactinomas in arteriosclerosis.</p> Graphical Abstract <p></p>

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Atherosclerosis enhances the efficacy of liposome-encapsulated bromocriptine in reducing the incidence of prolactinemia in pituitary tumors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月29日

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  • Zhe Zhang,
  • Guangyu Jia,
  • Qi Wang,
  • Yamei Yu,
  • Xiaolong Tang,
  • Heqing Zheng,
  • Xinyu Yang,
  • Yao Xiao,
  • Yangrui Ou,
  • Jingjing Jiang,
  • Hua Guo,
  • Ye Wang,
  • Shiyong Li

摘要

Intranasal drug delivery via nanocarriers has long been a research focus for enhancing drug concentration in the brain. However, the strategy of exploiting blood–brain barrier (BBB) alterations in atherosclerotic mouse models to enhance nanoparticle-mediated delivery of bromocriptine to the hypothalamus for the treatment of prolactinomas with hyperprolactinemia has not yet been reported. This study reveals that in patients with prolactinomas complicated by arteriosclerosis, bromocriptine therapy more effectively attenuates postoperative elevations in prolactin levels. In a mouse model, liposome-encapsulated bromocriptine efficiently traversed the nasal mucosa and entered the intracranial space. Compared with normal mice, bromocriptine-loaded liposomes delivered higher bromocriptine concentrations to the hypothalamus. Single-cell RNA sequencing revealed a significant upregulation of organic anion-transporting polypeptide 1a4 (Oatp1a4) expression in the brain endothelial cells of atherosclerotic mice. Importantly, bromocriptine-loaded liposomes more effectively reduced prolactin levels in a mouse model of prolactinoma with concurrent atherosclerosis. This study provides a theoretical foundation for the precision treatment of prolactinomas in arteriosclerosis.

Graphical Abstract