# Advances in hydrogen delivery strategies for therapeutic applications.
> 水素の送達戦略における最新の進展：治療応用に向けた包括的レビュー


## Abstract

Molecular hydrogen (H₂) exhibits selective antioxidant and anti-inflammatory activities, along with the capacity to regulate cellular signaling, metabolic pathways, and immune function. Evidence also points to anticancer effects mediated through modification of the tumor microenvironment and induction of apoptosis. Conventional administration routes—inhalation, oral hydrogen-rich water, and hydrogen-rich saline injection—are constrained by issues of stability, bioavailability, and site-specific delivery. This review systematically covers the mechanistic basis of H₂ action, encompassing redox regulation, inflammatory modulation, and tumor suppression, followed by an evaluation of existing delivery modalities and their limitations. Advanced solutions discussed include carrier-based H₂ systems, in situ generation via water-, acid-, and electrochemical reactions, and externally triggered platforms using photo-, sono-, and electrocatalysis for spatiotemporally controlled release. Microbiota-oriented strategies employing probiotics and prebiotics for sustained colonic H₂ production are also examined. Outstanding challenges—material scalability, biosafety, and clinical integration—and future interdisciplinary directions are highlighted.

### Mechanism

H₂ selectively scavenges reactive oxygen species and modulates redox signaling, suppresses pro-inflammatory cytokine production, and exerts antitumor effects by remodeling the tumor microenvironment and triggering apoptosis.

## Bibliographic

- **Authors**: Nguyen LD, Peng SY, Mac CH, Nguyen N, Lo SK, Lin PH, et al.
- **Journal**: Adv Drug Deliv Rev
- **Year**: 2026
- **PMID**: [41232804](https://pubmed.ncbi.nlm.nih.gov/41232804/)
- **DOI**: [10.1016/j.addr.2025.115734](https://doi.org/10.1016/j.addr.2025.115734)
- **Study type**: review
- **Delivery route**: mixed routes
- **Effect reported**: not assessed

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41232804. https://h2-papers.org/en/papers/41232804
> **Source**: PubMed PMID [41232804](https://pubmed.ncbi.nlm.nih.gov/41232804/)