Bentonite is characterized by a 2:1 layered structure with significant swelling capabilities, high surface area, and strong adsorptive and absorptive properties, contributing notably to its antimicrobial efficacy.^4,5 Kaolinite, a 1:1 layered clay mineral, historically revered for medicinal applications, typically exhibits limited intrinsic antimicrobial activity. Nevertheless, kaolinite’s exceptional adsorption capacity allows it to remove and immobilize harmful microbes, toxins, and other substances.^10,15,16

Despite numerous benefits, both bentonite and kaolinite carry certain health risks due to their potent adsorptive properties. Persistent inhalation, ingestion, or dermal absorption of these clays may result in the uptake of toxic elements, including heavy metals. For example, chronic exposure through soil (as seen with podoconiosis, associated with red volcanic clays) can result in severe dermatologic and systemic health complications.¹³ Thus, the therapeutic use of clays necessitates controlled preparation and adherence to stringent regulatory standards to mitigate potential toxicity.

Overall, the historical and contemporary significance of bentonite and kaolinite underlines their therapeutic potential and broad-spectrum antimicrobial activities. Recognizing their complex chemical interactions and dual nature—therapeutic yet potentially hazardous—is essential for harnessing their full medical and pharmaceutical potential.

Bentonite, composed largely of the smectite mineral montmorillonite, is characterized by a 2:1 layered silicate structure that enables high cation exchange capacity, swelling behavior, and surface reactivity. These factors underpin its broad-spectrum antimicrobial effects. In vitro studies demonstrate strong bactericidal activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, pathogens frequently implicated in dermatologic and wound infections.^5,18 Bentonite’s antimicrobial efficacy is mediated by several mechanisms including metal ions, ROS, pH, and redox potential modulation and adsorption. In one study, ZnO-bentonite nanocomposites reduced multidrug-resistant E. coli populations by 5-log within 24 hours while maintaining biocompatibility with human epithelial cell lines.¹⁸ These findings support bentonite’s potential in bioengineered wound dressings and topical antimicrobial formulations for dermatologic use.

Kaolinite is a 1:1 silicate clay with low cation exchange capacity and no significant swelling behavior. While it possesses minimal intrinsic bactericidal action, its adsorptive capacity supports skin barrier repair in inflammatory dermatoses.^4,13,15

Kaolinite has historically been used in dermatology as a base for masks and poultices for skin detoxification and seborrhea. Its efficacy improves when functionalized with antimicrobial agents. In a recent study, kaolinite impregnated with silver and zinc oxide nanoparticles demonstrated potent antimicrobial activity against Clostridium perfringens, E. coli, and coliform bacteria.¹⁹ These results suggest that kaolinite, while limited in native antibacterial potency, can be harnessed as a carrier for therapeutic agents in topical applications.

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While bentonite exhibits intrinsic antimicrobial and immunomodulatory activity, making it a promising candidate for wound dressings, hemostatic agents, and acne therapies, kaolinite plays a more adjunctive role serving as a biocompatible carrier and toxin-absorbing agent in dermatologic formulations.

The physical properties of clay have been observable both in ancient cultures and modern society - of note, their structure and ability to both absorb and adsorb impurities. The structure of these clays itself is of novel importance. Certain textures, such as fibrous needles can disrupt microbial cell membranes.²⁰ This propensity of clays to create a physical, surface attraction between itself and bacteria can have novel bactericidal properties.¹⁷ Bentonite’s antimicrobial efficacy is mediated by physical adsorption of bacterial toxins, reducing virulence and inflammation.^6,7,21,22 Kaolinite’s adsorptive capacity allows it to sequester inflammatory mediators, microbial toxins, and wound exudates.

These inherent properties are due in part to the small sizes of clays coupled with their asymmetric particle shapes. Collectively, this provides clays with an increased surface area, making adhesion to the surface of the skin a desirable quality in their utilization in wound care. In this manner, these clays can disrupt the ability of bacterial species to both passively and actively uptake nutrients. By doing so, there is a loss of integrity in the bacterial cellular envelopes in addition to the inability to transport metabolites, resulting in the accumulation of toxic compounds.¹³

Another method in which clays may demonstrate antibacterial activity is through chemical reactions. Due to the profound effect of clays to both absorb and adsorb that which they come into contact with, these clays can also be inundated with elements and minerals ubiquitous in the environment.⁴ Though this may vary considerably depending on the type of clay and location, they are typically impregnated with metallic ions, such as silver, copper, zinc, chromium, mercury, thallium, iron, aluminum, bismuth, silicon, and cadmium. Importantly, this provides these clays with novel bacteriostatic and/or bactericidal properties as cationic exchanges between the bacteria and clay can result in a derangement (and in some cases, arrest) of bacterial metabolism.²³

Bentonite’s antimicrobial efficacy is mediated by the following chemical mechanisms:

In addition to the endogenous release of these metals, clays also demonstrate antibacterial activity through lipid peroxidation and oxidative stress, which increase microbial membrane permeability. The production of intracellular hydroxyl radicals (formed during the Fenton reaction - the oxygenation of Fe²⁺) is effective in degrading protein and DNA.²⁰ The chemical properties of clays can prove to be useful in creating toxic environments for pathogenic microorganisms.¹³

While the combination of these attributes holds promising prospects in terms of clinical applications, it becomes imperative to consult the literature to inquire whether clays have shown efficacy against different types of microbial agents. In regard to the innate immune system, certain varieties of clay, namely sepiolite and palygorskite, have demonstrated antimyeloperoxidase activity, leading to the inhibition of neutrophil migration and edema. These properties are further facilitated by the low-genotoxicity of these clays on somatic and germ cells.²⁴

A study performed by Martsouka et al, compared the performance of bentonite, containing montmorillonite with copper and zinc, to both 1) unmodified bentonite and 2) bentonite with the added preservative, phenoxyethanol, as controls. In this study, the strength of these clays was compared against gram-positive bacteria, gram-negative bacteria, yeasts, and molds. The authors noted that clays impregnated with copper and zinc ions were immediately released after the samples were immersed in the solution. Compared to the controls, the zinc-containing bentonite did not inherently provide any antimicrobial activity of consequence against bacteria or molds but was effective against yeasts. However, the copper-containing bentonite did show excellent activity against bacteria and yeasts, while performing sufficiently with molds. The authors did conclude that a combination of clays could increase their antimicrobial activity while also serving as alternative options for human health applications.²⁵

In terms of wound healing, clays rich in silica can help stimulate collagen synthesis topically by acting as a catalyst in enzyme hydroxylation.²⁴ In both the past and present, silver ions have been useful as an antibacterial agent with added significance to its low cost, efficacy in smaller concentrations, and safer drug profile.²³ In conjunction with their anti-inflammatory and antibacterial properties, these clays have potential medical applications in wound dressings, where both silica and silver can be incorporated.

Such innovations provide an alternative form of treatment for bacterial infections, especially as antibiotic resistance becomes increasingly common. Multidrug-resistant strains of Mycobacterium species are of great public health concern. In particular, the rapid and spontaneous mutation rate of Mycobacterium tuberculosis necessitates research into further antibacterial agents to combat future increases in patient morbidity and mortality. Researchers have found that multidrug-resistant strains of Mycobacterium smegmatis to ampicillin and isoniazid provide a useful model for treating Mycobacterium tuberculosis species. Both iron mediated toxicity through reactive oxygen species formation and aluminum-mediated toxicity through bacterial membrane disruption were proven very promising against these Mycobacterium strains, especially when used synergistically with pyrazinamide.²⁶ This avenue of combination therapy offers great potential in treating not only Mycobacterium tuberculosis, but also other Mycobacterium, such as Mycobacterium marinum and Mycobacterium ulcerans.

Kaolinite is currently used clinically in products such as QuikClot Combat Gauze for hemostasis, Kerodex 51 as a barrier cream, and in sunscreens for its protective properties.²⁷ Clay-based nanocomposite hydrogels represent a class of materials for next-generation wound dressings due to their biocompatibility, moisture retention, antimicrobial action, and drug delivery capabilities. Kaolin, when combined with PVA polymer and penicillin-streptomycin, demonstrated effective antibacterial and hemostatic properties, along with positive swelling and absorption for wound applications. In comparison, bentonite used with chitosan or PVP polymers and silver sulfadiazine showed reduced toxicity, enhanced collagen deposition, and accelerated wound healing. Specifically, bentonite–chitosan–silver sulfadiazine nanocomposites exhibited strong bactericidal effects against Pseudomonas aeruginosa, suggesting potential for treating burn wounds where this multi-drug resistant organism is often found.²⁸

In a separate in vivo burn wound model utilizing Yucatan minipigs, a bentonite clay complex demonstrated anti-inflammatory effects, enhanced angiogenesis, cell proliferation, and improved collagen production, factors that collectively promote wound healing.²⁹

The use of clays for treating skin infections has also been explored through their role as carriers for antibiotics such as tetracycline and doxycycline. In one study, clay–antibiotic formulations effectively adsorbed and released these drugs, demonstrating antibacterial activity against Staphylococcus epidermidis, Cutibacterium acnes, and P. aeruginosa. These findings indicate a potential for developing topical treatments that could mitigate systemic side effects and combat rising antibiotic resistance. Among the clays tested, Laponite outperformed kaolinite and montmorillonite in terms of antibiotic loading, drug release, and antibacterial activity. It is worth noting that the clays used primarily contained sodium ions, which do not contribute to antibacterial effects, unlike other clays enriched with silver, copper, or zinc ions.³⁰

Another investigation assessed the antibacterial properties of natural and ion-exchanged clays— specifically kaolinite, two types of montmorillonite, and illite—in MRSA-infected wounds in mice models. Ion-exchanged illite clays exhibited the strongest antibacterial activity.³¹ The study highlights the variability in antibacterial efficacy among natural clays and suggests the potential to harness specific clay properties in standardized topical treatments for superficial infections.

In another study, salicylic acid was successfully incorporated into bentonite to create a nanocomposite suitable for dermatologic use. The bentonite–salicylic acid composite was found to be biocompatible, demonstrated low skin toxicity, and allowed for a delayed release of salicylic acid, enabling longer-lasting therapeutic effects.³²

A clinical study conducted in Shanghai in 2023 evaluated a facial clay mask containing kaolin, bentonite, cellulobeads, thermal spring water, and vitamin B5 in a group of 75 adults with oily or combination skin. Over four weeks of twice-weekly use, participants experienced a statistically significant reduction in acne lesions and skin oiliness, and improved hydration and skin barrier function.³³

Bentonite (montmorillonite) has also been studied for its potential use as a nanoclay drug delivery system in melanoma. In a study, doxorubicin was loaded into bentonite and it demonstrated sustained release over 21 days, supporting a role for local chemotherapy.³⁴ An in vitro and in vivo xenograft mouse model measured melanoma cell proliferation, viability, and nanoclay adhesion after treatment with a bentonite/palygorskite nanoclay complex. In vitro, cell survival was reduced in all clay treatment groups in a dose-dependent manner, and atomic force microscopy revealed high nonspecific adhesion of the nanoclay complex to melanoma cells compared to melanocytes. In vivo, the tumors treated with the nanoclay complex were smaller, weighed less, and had lower mitotic activity and necrosis. The nanoclays proved not to be cytotoxic to healthy cells as well.³⁵ Although the results are encouraging, further research including large-scale randomized clinical trials is necessary to confirm safety and efficacy in human populations.