脂质体给药地塞米松对小鼠脑外伤结果的改善与性别有关

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2024-02-04 DOI:10.1002/btm2.10647
Gherardo Baudo, Hannah Flinn, Morgan Holcomb, Anjana Tiwari, Sirena Soriano, Francesca Taraballi, Biana Godin, Assaf Zinger, Sonia Villapol
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引用次数: 0

摘要

创伤性脑损伤(TBI)会因其强烈的炎症反应引起的神经变性而对身体、情绪和认知造成长期影响。尽管康复护理取得了进展,但仍缺乏针对创伤性脑损伤患者的有效神经保护疗法。此外,目前治疗创伤性脑损伤的给药方法在靶向炎症脑区方面效率低下。为了解决这个问题,我们开发了一种包裹地塞米松(Dex)的脂质体纳米载体(Lipo),地塞米松是一种糖皮质激素受体激动剂,用于缓解各种情况下的炎症和肿胀。体外研究表明,人和小鼠神经细胞对 Lipo-Dex 的耐受性良好。脂多糖诱导神经发炎后,脂多糖对炎症细胞因子 IL-6 和 TNF-α 的释放有明显的抑制作用。此外,在控制性皮层撞击损伤(一种创伤性脑损伤模型)后,立即给年轻的成年雄性和雌性 C57BL/6 小鼠注射 Lipo-Dex。我们的研究结果表明,Lipo-Dex 可选择性地靶向损伤的大脑,从而减少病变体积、细胞死亡、星形胶质细胞增生、促炎细胞因子的释放以及小胶质细胞的活化。这凸显了在开发和评估治疗脑损伤的新型纳米疗法时将性别作为关键变量的重要性。这些结果表明,服用 Lipo-Dex 可有效治疗急性创伤性脑损伤。
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Sex-dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice

Traumatic brain injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-α, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after controlled cortical impact injury (a TBI model). Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of pro-inflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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