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负载褪黑素的纳米颗粒在冷冻保存过程中保护人类精子免受氧化应激。

Melatonin-loaded nanoparticles protecting human sperm from oxidative stress during cryopreservation.

作者信息

Xi Haitao, Gao Xue, Qiu Lin, Wang Yunzhi, Qiu Yifan, Tao Zihao, Hu Miyun, Jiang Xinyu, Yao Qing, Kou Longfa, Zhao Junzhao, Chen Ruijie

机构信息

Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Expert Opin Drug Deliv. 2025 Jul;22(7):1043-1055. doi: 10.1080/17425247.2025.2499117. Epub 2025 Apr 29.

Abstract

BACKGROUND

During the process of sperm cryopreservation, the overproduction of reactive oxygen species (ROS) triggers oxidative stress thereby leading to a reduction in sperm motility and quality. Therefore, it is a feasible strategy to mitigate oxidative damage during cryopreservation by adding antioxidants to freezing media.

RESEARCH DESIGN AND METHODS

In this study, we explored the potential of melatonin to protect sperm from oxidative stress-induced damage by evaluating sperm-related parameters after thawing through self-assembly with a hyaluronic acid-bilirubin conjugate into nanoparticles (M@HBn).

RESULTS

The optimized M@HBn exhibited uniform spherical morphology with average particle size of 112.57   ±   9.8 nm, PDI of 0.22   ±   0.02, a surface potential of  - 0.43   ±   1.02 mV and entrapment efficiency of 85.1   ±   4.6%. The addition of 5 μM M@HBn demonstrated a notable enhancement in frozen-thawed human spermatozoa viability, motility, and DNA integrity by scavenging ROS. Additionally, the use of M@HBn supplementation in freezing medium resulted in the most mitochondrial stability and total viability as compared to the other groups.

CONCLUSIONS

These findings suggest that M@HBn have the potential to serve as a novel drug delivery platform for protecting spermatozoa against from cryodamage while enhancing the quality of cryopreserved sperm and the bioavailability of melatonin.

摘要

背景

在精子冷冻保存过程中,活性氧(ROS)的过量产生会引发氧化应激,从而导致精子活力和质量下降。因此,在冷冻介质中添加抗氧化剂以减轻冷冻保存过程中的氧化损伤是一种可行的策略。

研究设计与方法

在本研究中,我们通过评估经透明质酸 - 胆红素共轭物自组装形成纳米颗粒(M@HBn)解冻后的精子相关参数,探索褪黑素保护精子免受氧化应激诱导损伤的潜力。

结果

优化后的M@HBn呈现均匀的球形形态,平均粒径为112.57 ± 9.8 nm,多分散指数(PDI)为0.22 ± 0.02,表面电位为 -0.43 ± 1.02 mV,包封率为85.1 ± 4.6%。添加5 μM M@HBn通过清除ROS显著提高了冻融后人精子的活力、运动能力和DNA完整性。此外,与其他组相比,在冷冻介质中使用M@HBn补充剂可使线粒体稳定性和总活力达到最佳。

结论

这些发现表明,M@HBn有潜力作为一种新型药物递送平台,保护精子免受冷冻损伤,同时提高冷冻保存精子的质量和褪黑素的生物利用度。

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