Nanobubbles (NBs) are ultrafine gas bubbles (~50–1000 nm diameter) in water that remain stable for days to months due to their low buoyancy and high surface charge (typically negative zeta potential from OH⁻ adsorption) and low buoyancy. Their large surface area and ability to carry gases (O₂, H₂, O₃, etc.) make them attractive for medical hydrotherapy. NBs significantly enhance the transdermal penetration of active ingredients.
The tiny bubbles (~110 nm) can traverse pores and deliver payload, whether an encapsulated gas or a dissolved drug, deep into tissues without chemical penetration enhancers. Preclinical and clinical observations indicate that NBs can improve blood oxygenation and wound healing, open wounds closed faster, biofilms (such as Staphylococcus/MRSA) were eradicated, and skin shedding and softening occurred. NBs can deliver dissolved O₂ deep into dermal and subdermal tissue layers (even systemically), potentially alleviating local hypoxia in chronic wounds or muscle. Hydrogen nanobubble baths markedly reduced systemic inflammation. In sum, nanobubble hydrotherapy is an emerging modality with intriguing physics and preliminary results.
In this analysis, we examine NB physics, biological interactions in hydrotherapy, and clinical evidence for hydrotherapy in wound healing, dermatology, pain, and rehabilitation
Biological Interactions in Hydrotherapy
Skin and Tissue Penetration: The ultrasmall size of NBs allows deeper skin penetration than plain water. Mitropoulos et al. (2023) showed oxygen NBs dramatically enhanced delivery of a model drug through a synthetic skin membrane (Franz cell experiments, a standard laboratory test for measuring skin absorption): the NB formulation delivered ~50% more active drug into the membrane than control solution. Mechanistically, as NBs approach the skin surface, their high stability (driven by neutral buoyancy and surface charge repulsion) keeps them active until they collapse near the tissue interface. This collapse generates localized microjets and shear forces that transiently and gently disrupt the stratum corneum (the outermost protective layer of the skin). This disruption, alongside penetration via follicular routes (through hair follicles and pores), allows NBs to effectively transport dissolved gases or active agents into the deeper dermal layers and underlying tissues. For hydrotherapy, this implies that therapeutic agents (such as antiseptics or drugs) added to an NB bath can reach target tissues far more efficiently.
Oxygenation and Wound Healing: Oxygen is critical to wound repair (for cellular metabolism and bacterial defense). Traditional topical oxygen (hyperbaric or local) is beneficial for hypoxic wounds. Oxygen NBs can elevate tissue O₂ without pressurization. In the ichthyosis case, NB baths “played a crucial role in open wounds’ healing and oxygenation of blood”. The nanobubbles reportedly accelerated wound closure and reduced biofilm in MRSA (Methicillin-Resistant Staphylococcus aureus, a strain of the bacterium that has become resistant to many commonly used antibiotics) infected skin. Although uncontrolled, this implies oxygen NBs promote angiogenesis/collagen and antimicrobial action. One cited mechanism: O₂ NBs are small enough to penetrate deeper and thus overcome skin hypoxia.
Antioxidant and Anti-inflammatory Effects: Hydrogen gas (H₂) is a recognized medical gas with antioxidant and anti-inflammatory properties. Nanobubble infusion greatly increases dissolved H₂ in water. Tanaka et al. (2022) treated healthy and autoimmune patients with a hydrogen-NB bath. They found “the HW [hydrogen-water] bath… has beneficial effects on serum antioxidant capacity, inflammation, and skin appearance.” In patients bathing repeatedly for weeks, baseline CRP dropped dramatically and symptoms improved markedly. These data suggest H₂-NBs can successfully mitigate systemic oxidative stress and inflammation trandermally.
Reactive Oxygen Species (ROS) Generation: Collapsing NBs can locally create ROS. This is exploited in water cleaning (where NBs with ultrasound create •OH radicals). In therapy, ozone NBs are a special case: ozone is deliberately bactericidal. A few reports (non-hydrotherapy) suggest ozone NB irrigation kills biofilms. The ichthyosis report cites ozone nanobubbles as antimicrobial. However, human exposure to ozone is limited by toxicity.
Conclusion
Nanobubble technology introduces a new dimension to hydrotherapy by combining the therapeutic benefits of water immersion with enhanced gas delivery and unique interfacial properties. Their small size, long stability, and high gas-loading capacity enable improved oxygen transport, enhanced transdermal delivery, and localized biological effects that are difficult to achieve with conventional hydrotherapy. Reported studies demonstrate promising outcomes in wound healing, skin regeneration, antimicrobial activity, inflammation reduction, and antioxidant enhancement, particularly when oxygen and hydrogen nanobubbles are used.
The ability to integrate nanobubbles into existing hydrotherapy systems without major infrastructure changes makes the technology attractive for clinical rehabilitation, dermatology, chronic wound management, and wellness applications. By improving tissue oxygenation, supporting skin repair, reducing oxidative stress, and enhancing the delivery of therapeutic agents, nanobubble hydrotherapy offers a safe and practical approach to advancing non-invasive treatment and rehabilitation.
References
- Nirmalkar, N., Pacek, A. W., & Barigou, M. (2018). On the existence and stability of bulk nanobubbles. Langmuir, 34(37), 10964–10973.
- Nirmalkar, N., Pacek, A. W., & Barigou, M. (2018). Interpreting the interfacial and colloidal stability of bulk nanobubbles. Soft Matter, 14, 9643–9656.
- Liu X, et al. Nanobubbles facilitate transdermal drug delivery through skin appendages. J Control Release. 2024
- Oehrl A, et al. Nanobubble hydrotherapy eradicates Staphylococcus aureus biofilms and accelerates healing. Journal Name. 2024
- Agarwal, A., Ng, W. J., & Liu, Y. (2011). Principle and applications of microbubble and nanobubble technology for water treatment. Chemosphere, 84(9), 1175–1180.
- Ushikubo, F. Y., et al. (2010). Evidence of the existence and the stability of nano-bubbles in water. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 361, 31–37.
- Alheshibri, M., Qian, J., Jehannin, M., & Craig, V. S. J. (2016). A history of nanobubbles. Langmuir, 32(43), 11086–11100.
- Temesgen, T., Bui, T. T., Han, M., Kim, T. I., & Park, H. (2017). Micro and nanobubble technologies as a new horizon for water treatment techniques: A review. Advances in Colloid and Interface Science, 246, 40–51.
- Ebina, K., et al. (2013). Oxygen and air nanobubble water solution promote osteoblast differentiation. International Journal of Nanomedicine, 8, 1413–1424.
- Becker, B. E. (2009). Aquatic therapy: Scientific foundations and clinical rehabilitation applications. PM&R, 1(9), 859–872.
- Wilcock, I. M., Cronin, J. B., & Hing, W. A. (2006). Physiological response to water immersion. Sports Medicine, 36(9), 747–765.
- Sen, C. K. (2009). Wound healing essentials: Let there be oxygen. Wound Repair and Regeneration, 17(1), 1–18.
- Journal of Controlled Release.
- World Health Organization (WHO). Guidelines for Drinking-water Quality.
- National Center for Biotechnology Information (NCBI). PubMed Database.