Enhanced antimicrobial activity and physicochemical stability of rapid pyro-fabricated silver-kaolinite nanocomposite.

The present research aims to enhance the antimicrobial activity of kaolinite surfaces by a one-step cost-effective and energy-efficient dry thermal reaction, producing an antibacterial and antifungal silver-kaolinite (Ag-Kao) nanocomposite agent. Pharmaceutical grade kaolin powder samples, with variable kaolinite structural order-disorder degree, were homogeneously mixed with silver nitrate in a proportion 1:4 AgNO3:kaolin (w/w) and sintered at 400 °C for 30 min. The composition, microstructure, microtexture and surface characteristics of the pyro-fabricated nanocomposites were characterized by XRD/XRF diffractometry, differential scanning calorimetry DSC, FT-IR spectroscopy, TEM/EDX, zeta potential (mV) measured within the 2-12 pH range, and BET method. Physicochemical stability was evaluated by silver dissociation testing under close-neutral and acidic conditions with Ag content assay using ICP-OES. The resulting Ag-Kao nanocomposites exhibited bulk silver contents ranging from 9.29% to 13.32% with high physicochemical stability in both neutral and acidic mediums (Ag dissociation rate <0.5% in 5 days). Ag nanocrystals exhibited particle sizes ranging from 5 to 30 nm, which were embedded and reinforced within the kaolinite matrix. The sizes of the Ag nanocrystals and their distribution patterns on the edges and faces of kaolinite platelets were controlled by the structural order-disorder degree. Highly ordered kaolinites (Hinckley Index, HI > 1) produced platelet edge-clustered silver nanocrystals due to the abundance of the dangling hydroxyls on platelet edges, while the highly disordered kaolinite (HI < 1) provided homogeneous platelet basal-doped silver nanocrystals due to the presence of some residual charges by exposed basal hydroxyl groups with interplatelet silver diffusivity. At pH 2, the magnitude of the positive surface charge was influenced by the silver nanocrystal size. Nanocomposites with the smallest silver nanocrystals (10-5 nm) exhibited the highest positive zeta potential (+15.2 mV to +17.0 mV), while those with larger silver nanocrystals (up to 30 nm) indicated lower positive zeta potential values (+9.5 mV to +3.6 mV). Under the same testing conditions using the Mueller-Hinton broth microdilution method, the raw kaolin samples did not show any significant antimicrobial activity, while all the pyro-fabricated Ag-Kao nanocomposite samples showed potent antibacterial and antifungal activity at low doses (MIC range 0.1-0.0125 mg/mL). Therefore, modulation of the effective electrostatic surface charge of the kaolinite platelets, via thermal doping of silver within their basal planes and edges, was found to be strongly dependent on the pH as well as the size and microtexture of the silver nanocrystals (mainly controlled by the order-disorder degree HI). The resulting modified nanostructure, with physicochemical stability and the efficient surface properties of the designed pyro-fabricated nanocomposite, led to an enhanced synergistic biophysical antimicrobial activity.

Kaolinite in pharmaceutics and biomedicine.

Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2µm (if compared to a human red blood cell of a typical diameter 6.2-8.2µm or to a virus particle of about 50nm diameter). The kaolinite platelets, either stacked together with a common booklet-like shape in a highly ordered structure (well crystallized) or disordered structure (poorly crystallized), consist of layers considered as a strong dipole of hydrophobic siloxane surface dominated by negative charges, and the other hydrophilic aluminol surface carries positive charges. Kaolinite has been used in many pharmaceutical applications as excipient or active ingredient, because it exhibits excellent physical, chemical and surface physicochemical properties. In addition to their classical pharmaceutical uses, kaolinite and its derivatives have been recently considered as a promising material in many biomedical innovation areas such as drug, protein and gene delivery based on the high interaction capacities with organic and biochemical molecules, bioadhesion and cellular uptake. Pharmaceutical kaolin grades are considerably demanded for usage as excipient in formulations of solid and semi-solid dosage forms. The most important functionalities of kaolin used as excipient are reported as diluent, binder, disintegrant, pelletizing and granulating, amorphizing, particle film coating, emulsifying and suspending agent. Because of its uninjured bioactivity, kaolinite has been also used as active agent for treatment of some common diseases. It can be topically administered as hemostatic agent, dermatological protector, anti-inflammatory agent and in pelotherapy, or orally as gastrointestinal protector, and antibacterial, antiviral, detoxification or antidiarrheal agent. With these premises, the future of kaolinite in health-care uses is strongly interesting, especially in the development of pharmaceutical and cosmetic industries. In biomedicinal investigations, it can be considered as a promising natural geomaterial for designing new derivatives that can contribute in the trials of discovering new therapeutic systems and treatment pathways of global challenge diseases such as cancer, viruses, antibiotic resistant bacteria, alzheimer, chronic skeletomuscular and geriatric diseases.

Folk pharmaceutical formulations in western Mediterranean: identification and safety of clays used in pelotherapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Clays are naturally occurring ingredients of many natural health products, being included in most of ancient Mediterranean/European medical texts and currently used to prepare therapeutic hot-muds (peloids) in several thermal stations of the Mediterranean region. Clays are included in the formulation of peloids as vehicles of the mineral-medicinal water, to obtain inorganic gels with rheological and thermal properties suitable to be topically applied. Knowledge about formulations and preparation procedures of these traditional medicines has been orally transmitted since ancient times. Increasing recognition of the therapeutic utility of these traditional and natural health care substances make necessary a full ethnopharmaceutic research to ascertain those compositional characters that allow to establish quality attributes and corresponding requirements for these materials and products, including identity, purity, richness and safety. MATERIALS AND METHODS: Five clay samples (A, B, C, D and E) currently used in various spa centers of southern European/Mediterranean countries were studied. X-Ray diffraction (XRD) and X-ray fluorescence (XRF) data were used to asses sample identity and richness. Elemental impurities and microbiological contaminants were also determined and compared to normative limits. Particle size distribution was related to their safety as powder materials. RESULTS: Samples A, C, D and E were identified as "high purity clay", while sample B was identified as a mix of clay minerals and carbonates. The presence of carbonates in this sample could compromise its suitability for pelotherapy. The studied clays meet the main normative limits for metals impurities, with the exception of arsenic in sample A and nickel in sample B. The samples comply with the microbiological limits proposed by European legislation for medicinal products. According to the particle size of the studied samples, prevention and control of dust exposure must be considered. CONCLUSIONS: Despite their demonstrated longevity, the use of clays in traditional medicine formulations as peloids greatly requires comprehension of their identity and safety attributes. Continuity of these mineral substances as recognized health care ingredients oblige to conduct interdisciplinary research to know the features that sustain their traditional use in the preparation of medicines (ethnopharmaceutics).