Overcoming Biological Barriers: A Comprehensive Review of Advanced Melatonin Delivery Systems for Therapeutic Applications
- 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China
- 2The State Key Laboratory of Fluid Power and Mechatronic Systems & School of Mechanical Engineering, Zhejiang University, Hangzhou 310028, China
Abstract
Melatonin is a pleiotropic hormone with well-documented antioxidant, anti-inflammatory, neuroprotective, and immunomodulatory properties, making it a promising candidate for the treatment of diverse diseases including neurodegenerative disorders, cardiovascular diseases, cancer, and sleep disturbances. However, its clinical translation has been hampered by several biopharmaceutical limitations, including poor aqueous solubility, extensive hepatic first-pass metabolism, rapid systemic clearance, and low oral bioavailability. Additionally, physiological barriers such as the blood-brain barrier, stratum corneum, and mucosal epithelia restrict its accumulation at target sites. In recent years, nanotechnology-based drug delivery systems have emerged as powerful tools to overcome these challenges. This review provides a comprehensive overview of advanced melatonin nanocarriers with a focus on their design principles, formulation strategies, and therapeutic applications. A central theme of this review is the integration of carrier design with biological barrier circumvention and administration routes-elucidating how specific nanocarrier platforms address the shortcomings of conventional immediate- and prolonged-release melatonin formulations through spatial and temporal control over drug distribution. We summarize recent preclinical progress in melatonin nanocarriers for a wide range of disease models, including Alzheimer's disease, Parkinson's disease, myocardial infarction, retinal degeneration and glaucoma, depression, and various cancers, with emphasis on the relationship between administration routes and therapeutic outcomes. Finally, critical challenges in clinical translation are addressed, including large-scale manufacturing, long-term toxicity evaluation, regulatory considerations, and the development of chronotherapy-compatible delivery systems. By integrating insights from materials science, pharmaceutics, and nanomedicine, this review aims to provide a rational framework for the future design and clinical application of melatonin-based nanotherapeutics.
Related
- The next frontier in transplantation: overcoming biological barriers and logistical limitations.
- Establishing an in Vitro Model of Astrocyte Activation in Ischemic Traumatic Brain Injury: Therapeutic Synergy of Melatonin and Oxygen Nanobubbles
- Design, synthesis and biological evaluation of novel artemisinin derivatives as potent P-glycoprotein modulators for overcoming multidrug resistance.
- Cardiac Fibrosis as a Dynamic Therapeutic Target: Overcoming Translational Barriers to Antifibrotic Therapy.
- Machine Learning and Deep Learning for Early Disease Detection Across Modalities: A Comprehensive Review of Methods, Applications, and Clinical Translation
BibTeX
@article{yang2026overcoming,
title = {{Overcoming Biological Barriers: A Comprehensive Review of Advanced Melatonin Delivery Systems for Therapeutic Applications}},
author = {Zhenyu Yang and Yiduo Chen and Shaoying Li and Xiaoyue Lei and Xincheng Wu and Yuan Wang and Shuli Deng},
journal = {International Journal of Medical Sciences},
year = {2026},
month = jun,
doi = {10.7150/ijms.134841},
url = {https://doi.org/10.7150/ijms.134841},
note = {CC BY},
}
RIS
TY - JOUR
TI - Overcoming Biological Barriers: A Comprehensive Review of Advanced Melatonin Delivery Systems for Therapeutic Applications
AU - Zhenyu Yang
AU - Yiduo Chen
AU - Shaoying Li
AU - Xiaoyue Lei
AU - Xincheng Wu
AU - Yuan Wang
AU - Shuli Deng
PY - 2026
DA - 2026/06/10
JO - International Journal of Medical Sciences
DO - 10.7150/ijms.134841
UR - https://doi.org/10.7150/ijms.134841
AB - Melatonin is a pleiotropic hormone with well-documented antioxidant, anti-inflammatory, neuroprotective, and immunomodulatory properties, making it a promising candidate for the treatment of diverse diseases including neurodegenerative disorders, cardiovascular diseases, cancer, and sleep disturbances. However, its clinical translation has been hampered by several biopharmaceutical limitations, including poor aqueous solubility, extensive hepatic first-pass metabolism, rapid systemic clearance, and low oral bioavailability. Additionally, physiological barriers such as the blood-brain barrier, stratum corneum, and mucosal epithelia restrict its accumulation at target sites. In recent years, nanotechnology-based drug delivery systems have emerged as powerful tools to overcome these challenges. This review provides a comprehensive overview of advanced melatonin nanocarriers with a focus on their design principles, formulation strategies, and therapeutic applications. A central theme of this review is the integration of carrier design with biological barrier circumvention and administration routes-elucidating how specific nanocarrier platforms address the shortcomings of conventional immediate- and prolonged-release melatonin formulations through spatial and temporal control over drug distribution. We summarize recent preclinical progress in melatonin nanocarriers for a wide range of disease models, including Alzheimer's disease, Parkinson's disease, myocardial infarction, retinal degeneration and glaucoma, depression, and various cancers, with emphasis on the relationship between administration routes and therapeutic outcomes. Finally, critical challenges in clinical translation are addressed, including large-scale manufacturing, long-term toxicity evaluation, regulatory considerations, and the development of chronotherapy-compatible delivery systems. By integrating insights from materials science, pharmaceutics, and nanomedicine, this review aims to provide a rational framework for the future design and clinical application of melatonin-based nanotherapeutics.
SN - 1449-1907
ER -