Background. The present work aims at formulating the melatonin-loaded nanoparticles (MTNPs) exhibiting the controlled-release and pH-sensitivity to repurpose the use of melatonin in the treatment of depressive-like behaviors and hypothalamus-pituitary-adrenal (HPA) axis dysregulation. Methods. MTNPs were characterized for the size, drug incorporation, and in vitro release in the different pH environments. Its merits were in vivo tested on the pinealectomized rats presenting the depressive-like behaviors and the abnormal HPA axis activity by calculating the improvement on saccharin preference, swimming immobility time, and the negative feedback of HPA axis. Results. Results revealed that MTNPs showed nanometer size, 15.77% of drug loading, 33.82% of encapsulation efficiency, the different controlled-release profiles in different pH environments (pH 1.2, pH 6.8, and pH 7.4), more sensitivity release in simulated intestinal fluid (pH 7.4) and blood (pH 6.8), and less sensitivity release in simulated gastric fluid (pH 1.2). Furthermore, MTNPs displayed better antidepressant actions in reducing the immobility time of forced swimming test, increasing the preference for saccharin, and sensitizing the blunt negative feedback of HPA axis, when compared to the free melatonin. Conclusions. The controlled-release nanoparticles is shown to be an effective improvement on the dosage form for melatonin, which is worthy of futuristic and complete evaluation.

中文翻译：

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用于增强抗抑郁作用和 HPA 激素调节的负载褪黑激素的纳米颗粒

背景。目前的工作旨在配制具有控释和 pH 敏感性的负载褪黑激素的纳米颗粒 (MTNPs)，以重新利用褪黑激素治疗抑郁样行为和下丘脑-垂体-肾上腺 (HPA) 轴失调。方法。MTNPs 的特点是大小、药物掺入和在不同 pH 环境中的体外释放。通过计算糖精偏好、游泳不动时间和HPA轴负反馈的改善，在松果体切除后出现抑郁样行为和异常HPA轴活动的大鼠体内测试其优点。结果。结果表明，MTNPs 具有纳米级尺寸，载药量为 15.77%，包封率为 33.82%，不同 pH 环境（pH 1.2、pH 6.8 和 pH 7.4）下的控释曲线不同，在模拟肠液（pH 7.4）和血液（pH 6.8）中释放更敏感，在模拟胃液（pH 6.8）中释放更敏感1.2)。此外，与游离褪黑激素相比，MTNPs 在减少强迫游泳测试的不动时间、增加对糖精的偏好和敏感化 HPA 轴的钝性负反馈方面显示出更好的抗抑郁作用。结论。控释纳米颗粒被证明是对褪黑激素剂型的有效改进，值得未来和完整的评估。此外，与游离褪黑激素相比，MTNPs 在减少强迫游泳测试的不动时间、增加对糖精的偏好和敏感化 HPA 轴的钝性负反馈方面显示出更好的抗抑郁作用。结论。控释纳米颗粒被证明是对褪黑激素剂型的有效改进，值得未来和完整的评估。此外，与游离褪黑激素相比，MTNPs 在减少强迫游泳测试的不动时间、增加对糖精的偏好和敏感化 HPA 轴的钝性负反馈方面显示出更好的抗抑郁作用。结论。控释纳米颗粒被证明是对褪黑激素剂型的有效改进，值得未来和完整的评估。