Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard les...

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Main Authors: Haitao Xi, Lihui Huang, Lin Qiu, Shize Li, Yuqi Yan, Yang Ding, Yuhao Zhu, Fugen Wu, Xianbao Shi, Junzhao Zhao, Ruijie Chen, Qing Yao, Longfa Kou
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:International Journal of Pharmaceutics: X
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590156724000409
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author Haitao Xi
Lihui Huang
Lin Qiu
Shize Li
Yuqi Yan
Yang Ding
Yuhao Zhu
Fugen Wu
Xianbao Shi
Junzhao Zhao
Ruijie Chen
Qing Yao
Longfa Kou
author_facet Haitao Xi
Lihui Huang
Lin Qiu
Shize Li
Yuqi Yan
Yang Ding
Yuhao Zhu
Fugen Wu
Xianbao Shi
Junzhao Zhao
Ruijie Chen
Qing Yao
Longfa Kou
author_sort Haitao Xi
collection DOAJ
description In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.
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spelling doaj-art-311b4d02b9134c68af966a20b4c2d7e32025-08-20T01:58:11ZengElsevierInternational Journal of Pharmaceutics: X2590-15672024-12-01810026810.1016/j.ijpx.2024.100268Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniquesHaitao Xi0Lihui Huang1Lin Qiu2Shize Li3Yuqi Yan4Yang Ding5Yuhao Zhu6Fugen Wu7Xianbao Shi8Junzhao Zhao9Ruijie Chen10Qing Yao11Longfa Kou12Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Pediatric, The First People's Hospital of Wenling, Taizhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, ChinaReproductive Medicine Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Corresponding authors at: Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325027, China; Corresponding authors at: Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.http://www.sciencedirect.com/science/article/pii/S2590156724000409OocytesIn vitro maturationReactive oxygen speciesMelatoninBilirubinCationic nanoparticles
spellingShingle Haitao Xi
Lihui Huang
Lin Qiu
Shize Li
Yuqi Yan
Yang Ding
Yuhao Zhu
Fugen Wu
Xianbao Shi
Junzhao Zhao
Ruijie Chen
Qing Yao
Longfa Kou
Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
International Journal of Pharmaceutics: X
Oocytes
In vitro maturation
Reactive oxygen species
Melatonin
Bilirubin
Cationic nanoparticles
title Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
title_full Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
title_fullStr Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
title_full_unstemmed Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
title_short Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques
title_sort enhancing oocyte in vitro maturation and quality by melatonin bilirubin cationic nanoparticles a promising strategy for assisted reproduction techniques
topic Oocytes
In vitro maturation
Reactive oxygen species
Melatonin
Bilirubin
Cationic nanoparticles
url http://www.sciencedirect.com/science/article/pii/S2590156724000409
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