Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (26): 6930-6936.doi: 10.12307/2026.737

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Development and application of natural oral hydrogels in drug delivery systems

Yang Qi1, Xiang Xi1, Wang Han2, Zou Zhen3, Zhang Lunci2, Mireadeli·Abulimiti2, Liao Yue1, Li Xinzhi2, 3

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  1. 1School of Basic Medicine, 3School of Health Sciences, China Three Gorges University, Yichang 443002, Hubei Province, China; 2Renhe Hospital Affiliated to China Three Gorges University, Yichang 443099, Hubei Province, China
  • Accepted:2025-09-01 Online:2026-09-18 Published:2026-03-16
  • Contact: Liao Yue, MD, School of Basic Medicine, China Three Gorges University, Yichang 443002, Hubei Province, China Li Xinzhi, MD, Professor, Renhe Hospital Affiliated to China Three Gorges University, Yichang 443099, Hubei Province, China; School of Health Sciences, China Three Gorges University, Yichang 443002, Hubei Province, China
  • About author:Yang Qi, MS candidate, School of Basic Medicine, China Three Gorges University, Yichang 443002, Hubei Province, China
  • Supported by:
    Open Foundation of Hubei Province Key Laboratory of Tumor Microenvironment and Immunotherapy, No. 2023KZL07 (to LY); Yichang Medical and Health Research Project, No. A24-2-059 (to LY); Talent Research Startup Fund of China Three Gorges University, No. 2023RCKJ013 (to LY); National Natural Science Foundation of China (Top-level Project), No. 81871956 (to LXZ); Science and Technology Development Project of Chinese Association of Rehabilitation Medicine, No. 2023132-55 (to LXZ)

Abstract: BACKGROUND: Oral drug delivery has consistently been the most preferred route of administration due to its high patient compliance, significantly enhancing the overall treatment experience compared to injectables. However, the gastrointestinal environment severely limits drug bioavailability. As the demand for biocompatibility and biodegradability in the medical field continues to grow, natural hydrogels have emerged as ideal drug delivery carriers, attracting widespread attention.
OBJECTIVE: To explore the development and application of oral hydrogels made from various natural materials, from material selection to synthesis methods.
METHODS: A comprehensive literature search was conducted in the PubMed and Web of Science databases using the English search terms “oral hydrogels, physical crosslinking, chemical crosslinking, natural material, therapy, drug delivery, application of disease research” to identify the most recent relevant articles published from 2009 to 2024. A total of 83 articles were selected for review.
RESULTS AND CONCLUSION: Hydrogels, as a promising new drug delivery system, exhibit significant advantages in achieving precise drug delivery and controlled release. Oral natural hydrogels stand out in the field of drug delivery due to their excellent biocompatibility, good biodegradability, and extremely low potential toxicity. They not only enable precise drug delivery but also effectively avoid irritation caused by direct contact between the drug and the gastrointestinal tract, providing a safer and more effective route for drug delivery. With the tireless exploration of researchers, new intelligent hydrogel delivery systems based on natural materials are constantly emerging, such as pectin-based pH-responsive hydrogels and hyaluronic acid-based reactive oxygen species-responsive hydrogels. These new materials have opened up new avenues for intelligent and precise drug delivery. However, the application of natural hydrogels has also exposed some unresolved issues. On the one hand, natural materials generally suffer from insufficient mechanical properties and tensile strength, making them difficult to meet complex drug delivery requirements. On the other hand, despite their natural origin, natural materials can still trigger immune responses in the human body.

Key words: natural material, natural polymer, natural small molecule, oral administration, hydrogel, drug delivery, crosslinking method, disease application, biomaterial

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