Halloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

The use, in veterinary practice, of a three-dimensional biopolymer matrix (based on chitosan, agarose, and gelatin and doped with halloysite nanotubes) as a vehicle for mesenchymal stem cells (MSCs) to repair bone defects is reported here. The nanocomposite, combined with allogenic adipose-derived stem cells, was suitable for the repair of bone defects in dogs when paired with standard surgery involving metal Kirshner wires. The absence of inflammatory reactions to biopolymer matrices with allogenic stem cells was revealed in the case of an animal prone to inflammatory and allergic reactions. In addition, positive dynamics in the fusion of chronic bone defects without rejection reactions was observed after using a biopolymer matrix with MSCs.

The ongoing pandemic, COVID-19 (SARS-CoV-2), has afflicted millions of people around the world, necessitating that the scientific community work, diligently and promptly, on suitable medicaments. Although vaccination programs have been run globally, the new variants of COVID-19 make it difficult to restrict the spread of the virus by vaccination alone. The combination of vaccination with anti-viral drug formulation is an ideal strategy for tackling the current pandemic situation. Drugs approved by the United States Food and Drug Administration (FDA), such as Remdesivir, have been found to be of little or no benefit. On the other hand, re-purposing of FDA-approved drugs, such as niclosamide (NIC), has offered promise but its applicability is limited due to its poor aqueous solubility and, therefore, low bioavailability. With advanced nano-pharmaceutical approaches, re-purposing this drug in a suitable drug-carrier for a better outcome may be possible. In the current study, an attempt was made to explore the loading of NIC into exfoliated layered double hydroxide nanoparticles (X-LDH NPs); prepared NIC-X-LDH NPs were further modified with eudragit S100 (ES100), an enteric coating polymer, to make the final product, ES100-NIC-X-LDH NPs, to improve absorption by the gastro/intestinal tract (GIT). Furthermore, Tween 60 was added as a coating on ES100-NIC-X-LDH NPs, not just to enhance its in vitro and in vivo stability, but also to enhance its mucoadhesive property, and to obtain, ultimately, better in vivo pharmacokinetic (PK) parameters upon oral administration. Release of NIC from Tween 60-ES100-NIC-X-LDH NPs was found to be greater under gastro/intestinal solution within a shorter period of time than the uncoated samples. The in vivo analysis revealed that Tween 60-ES100-NIC-X-LDH NPs were able to maintain a therapeutically relevant NIC plasma concentration in terms of PK parameters compared to the commercially available Yomesan®, proving that the new formulation might prove to be an effective oral drug-delivery system to deal with the SARS-CoV-2 viral infections. Further studies are required to ensure their safety and anti-viral efficacy.

The number of studies of controlled drug-release systems is growing constantly. Bionanocomposite materials which can be prepared from the combination of biopolymers with inorganic solids such as clay minerals offer interesting alternatives for use as drug-delivery systems. In the present study, new bionanocomposite drug-release systems were prepared from the intercalation of the antibiotic drug ciprofloxacin into montmorillonite using an ion-exchange reaction. In order to prepare more stable systems for oral ciprofloxacin release, this ciprofloxacin-clay intercalation compound was incorporated into i-carrageenan-gelatin biopolymer blend to produce bionanocomposite materials. Bionanocomposites of two distinct i-carrageenan and gelatin mass ratios were conformed as beads through an ionic gelification reaction with Ca2+ ions, and dried by freeze-drying where liquid nitrogen or conventional freezing was adopted in the freezing step. The resulting ciprofloxacin-clay hybrid was characterized by X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy, solid state 13C Nuclear Magnetic Resonance (NMR), thermal analysis, and scanning electron microscopy (SEM). The montmorillonite-ciprofloxacin hybrid incorporated into the bionanocomposite beads was evaluated by in vitro release studies which showed a significant difference in the release profiles in the aqueous medium used to simulate the gastrointestinal tract, depending on the blend composition and the freezing method employed in the preparation of the beads. The results point to bionanocomposite systems based on ciprofloxacin-clay hybrids and biopolymers that may be used as devices in the biomedical area.

Clays are used in various cosmetic formulations, such as sunscreens, toothpastes, deodorants, creams, hair cosmetics, makeups, nail polish, facial masks, and shampoos, among others, to improve the organoleptic and physicochemical characteristics, to increase the stability, or to facilitate elaboration. Together with their technological functionalities, clays are cosmetologically active ingredients with cleaning, anti-aging, anti-wrinkling, and sun-care functionalities. Talc, kaolinite, mica, and some smectites are the clay minerals used most frequently in cosmetic products, but several other phyllosilicates as well as modified and synthetic clays are also used. Sometimes, clays are useful in the design of cosmetics just because they are made of rigid, small, and anisometric particles. Kaolinite and mica are made of hard prismatic particles which are lightly abrasive over the skin, teeth, or hair. Electric charges in smectites result in ion-exchange capacities useful in the loading of active cosmetics but also adsorbing and cleaning waste substances. Intermediate net negative charges of smectites result in layer expansion in polar media and specific rheological properties that are very useful in cosmetic formulations. The absence of charged particles in talc and kaolin make them flow easily resulting in lubricant effects. Protection against radiation from the sun by clay particles and decorative effects complete the possibilities of clays in cosmetics. The nomenclature for clays used as ingredients in cosmetics follows historical use and the names of commercial products, rather than following strict compositional principles. In this sense, an effort was made here to correlate the names of the minerals that make up each of the clay-based cosmetic ingredients.

The present study introduces an overview of gentamicin-clay mineral systems for applications in biomedicine and then focuses on the development of a series of gentamicin/clay hybrid materials to be used as the bioactive phase of hydroxypropylmethylcellulose (HPMC) to produce bionanocomposite membranes possessing antimicrobial activity of interest in wound-dressing applications. Gentamicin (Gt) was adsorbed from aqueous solutions into a montmorillonite (Cloisite®-Na+) to produce intercalation compounds with tunable content of the antibiotic. The hybrids were characterized by CHN chemical analysis, energy-dispersive X-ray analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis, confirming the intercalation of Gt by an ion-exchange mechanism. The release of Gt from the hybrids was tested in water and in buffer solution to check their stability. Hybrids with various amounts of Gt were incorporated into a HPMC matrix at various loadings and processed as films by the casting method. The resulting Gt-clay/HPMC bionanocomposites were characterized by means of field-emission scanning electron microscopy, and were also evaluated for their water-adsorption and mechanical properties to confirm their suitability for wound-dressing applications. The antimicrobial activity of the bionanocomposite films was tested in vitro toward various microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium, Acinetobacter baumannii, and Klebsiella pneumonia), showing a complete bacterial reduction even in films with small Gt contents.

The overuse of antibiotics in medicine has led to concerns over management of wound infections where antibiotic-resistant bacteria are involved. Wound infections exhibit both acquired and biofilm-associated antibiotic resistance; innovative non-antibiotic therapeutic and preventive treatments are needed to limit emergence of conventional antimicrobial resistance and to address biofilm-associated resistance. Toward this goal, natural antibacterial clays have been identified that are effective at killing drug-resistant human pathogens in planktonic and biofilm states, in vitro. To move toward clinical testing of antibacterial clays, the present study was conducted to evaluate the topical application of a natural antibacterial clay to wounds in mice experimentally infected with methicillin-resistant Staphylococcus aureus (MRSA). Five preliminary animal trials were conducted to test various methods of applying hydrated antibacterial clay to infected wounds. None of the experiments yielded significantly reduced MRSA infection in vivo, compared to controls. Several hypotheses were tested to explore the diminished clay antibacterial activity in vivo including: (1) pH and Eh of mineral-bacterial suspensions may differ in wound fluids compared to growth media; (2) antibacterial reactants may complex with components of the wound; (3) hydrated clays may dry out in the wound; and (4) limited dissolved oxygen may reduce Fenton reactions. Ancillary in vitro tests were performed to explore these hypotheses. Results indicate that the clay application to wounds may require enhanced oxidation and possibly a longer treatment regimen. The experimental results foster understanding of the natural clay–bacterial interactions in wounds and may improve designs for medicinal applications.

Epilepsy treatment requires anti-seizure medical formulations; available medications have various painful side effects and penetrate the brain–blood barrier poorly. A promising method is the use of natural clay nanocontainers for drug delivery through this membrane barrier. Halloysites (Hly) are biocompatible, 50-nm diameter tubes with a positively charged, hollow inner lumen and negatively charged outer shell and are available naturally. These characteristics enable them to be versatile as drug loaded ‘nano-torpedoes’ effectively penetrating cell membranes. The endothelial cells are a major cell type in the blood–brain barrier that provides for the selective permeability separating the circulating blood and allowing only the passage of glucose, water, and amino acids, but not traditional drug formulations. Nanotubes encapsulating rhodamine isothiocyanate and ionomycin penetration through the rat-brain microvascular endothelial cells followed by a prolonged 24-h drug release was demonstrated. A model membrane was set up across 0.4-μm-pore polystyrene transwell supports covered by seeding endothelial and astrocyte cells to mimic the blood–brain barrier in vivo. This barrier demonstrated a dual permeation mechanism (inter-cell accumulation and through-passing) for loaded Hlys, exploiting the potential of this nanoclay in the trans-membrane delivery of drugs. Use of Hly nanotubes as drug carriers to penetrate the brain microvascular endothelial barrier and to deliver the payload displayed a new approach for the treatment of brain diseases such as epilepsy.

Clay, or more precisely, certain clay typologies, have been used traditionally by humans for therapeutic, nutritional, and skin-care purposes though they may be responsible for some relatively rare but significant health and skin-care risks. For example, clay particles could adsorb and make available for elimination or excretion any potential toxic elements or toxins being ingested or produced, but they could also adsorb and make available for incorporation, through ingestion or through dermal absorption, toxic elements, e.g. heavy metals. Geophagy has been observed in all parts of the world since Antiquity, reflecting cultural practices, religious beliefs, and physiological needs, be they nutritional (dietary supplementation) or as a remedy for disease. Some clays and clay minerals are employed widely in both the pharmaceutical and cosmetics industries as active compounds/agents and as excipients. In the biomedical field, some clay minerals such as halloysite and montmorillonite are known for their effective role as carriers for the control and sustainable delivery of active drug molecules, and in the biomaterials field some clay minerals are used for scaffold, hydrogel, foam, and film production. Constraints, both chemical and microbiological, on the use of clay-based products for therapeutic and cosmetic topical applications are generally imposed by sanitary regulations, and some solutions are proposed herein to control and reduce such restrictions. Particular emphasis is placed here on peloids and pelotherapy, as well as on manipulated and modified peloids, and specifically on tailored peloids or ‘designed and engineered’ peloids, and their derivatives, bactericidal peloids and ointments. As far as the so-called ‘killer clays’ are concerned, their pre-requisites, mechanisms of action, and disinfection role are also enhanced. Podoconiosis is an environment-related or geochemical disease that occurs in tropical highland areas, and is caused by long-term exposure of bare feet to volcanic, red-clay soil and affects some people, particularly those working in agriculture in some regions of Africa, Asia, and South America.

DNA manipulation is crucial for many biotechnological prospects and for medical applications such as gene therapy. This requires the amplification and extraction of DNA from bacteria and the transfer of these DNA molecules into cells, including bacterial and mammalian cells. The capacity of the natural magnesium silicate clay mineral sepiolite to bind to DNA makes it a potentially useful tool for biotechnological/medical strategies. In addition, sepiolite is inexpensive and classified as non-toxic and non-carcinogenic. This review will first describe the physicochemical interactions between sepiolite and DNA. Then, the leverage of sepiolite/DNA interactions for DNA extraction from bacteria, to optimize DNA transfer into bacteria and DNA transfection into mammalian cells, are presented. Finally, the putative toxicity of sepiolite and its advantages and perspectives for future prospects, such as the improvement of immunotherapy, are also discussed.

Anthropogenic activity releases hazardous contaminants and pollutants that are not removed fully by water treatments. Among such pollutants, bisphenol-A (BPA) and bisphenol-S (BPS) are included in a series of Endocrine Disruptive Compounds, which may cause disruption due to hormone blockage or mimicking. Thus, even though those pollutants are not considered lethal, they are hazardous to health due to their similarity to 17β-estradiol, and they have been shown to cause developmental malformation in Zebrafish and breast and prostate tumors in rodents. Both BPA and BPS have been found in water sources at concentrations >30 μg L–1 and since water treatment plants are ineffective at removing them, their concentration is constantly increasing. The purpose of the present study, using a collection of experiments performed by B.Sc. and M.Sc. students, was to apply clay-based materials to the removal of such health hazards from water. Specifically adapted modified clays as neutral organoclays can optimize the interaction between pollutants and the matrix to achieve efficient adsorption. Such an approach is very effective for relatively insoluble pollutants such as BPA, but less so for the more soluble BPS. On the other hand, BPS can be photodegraded catalytically using raw clay or TiO2-impregnated clay. At low catalyst concentration, the modified clay was as effective as a commercial TiO2 catalyst, whereas combining it with H2O2 yielded considerably better results. In summary, clay minerals offer solutions for the removal of health-hazardous pollutants from water, based on different procedures and mechanisms. The versality of clay minerals allows 'tailoring' specifically adapted materials that might improve their efficiency based on such very specific pollutant-matrix interactions.