Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy.

Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

Interaction of Pseudomonas putida with kaolinite and montmorillonite: a combination study by equilibrium adsorption, ITC, SEM and FTIR.

Equilibrium adsorption along with isothermal titration calorimetry (ITC), Fourier transform infrared spectra (FTIR) and scanning electron microscopy (SEM) techniques were employed to investigate the adsorption of Pseudomonas putida on kaolinite and montmorillonite. A higher affinity as well as larger amounts of adsorption of P. putida was found on kaolinite. The majority of sorbed bacterial cells (88.7%) could be released by water from montmorillonite, while only a small proportion (9.3%) of bacteria desorbed from kaolinite surface. More bacterial cells were observed to form aggregates with kaolinite, while fewer cells were within the larger bacteria-montmorillonite particles. The sorption of bacteria on kaolinite was enthalpically more favorable than that on montmorillonite. Based on our findings, it is proposed that the non-electrostatic forces other than electrostatic force play a more important role in bacterial adsorption by kaolinite and montmorillonite. Adsorption of bacteria on clay minerals resulted in obvious shifts of infrared absorption bands of water molecules, showing the importance of hydrogen bonding in bacteria-clay mineral adsorption. The enthalpies of -4.1+/-2.1 x 10(-8) and -2.5+/-1.4 x 10(-8)mJ cell(-1) for the adsorption of bacteria on kaolinite and montmorillonite, respectively, at 25 degrees C and pH 7.0 were firstly reported in this paper. The enthalpy of bacteria-mineral adsorption was higher than that reported previously for bacteria-biomolecule interaction but lower than that of bacterial coaggregation. The bacteria-mineral adsorption enthalpies increased at higher temperature, suggesting that the enthalpy-entropy compensation mechanism could be involved in the adsorption of P. putida on clay minerals. Data obtained in this study would provide valuable information for a better understanding of the mechanisms of mineral-microorganism interactions in soil and associated environments.

[Desorption of kaolin adsorbed copper in the fish gill microenvironment].

In order to investigate the bioavailability of kaolin adsorbed copper on gills of carpio, and to explain its possible mechanism in terms of speciation, exposure experiments with constant concentration of water soluble copper and increased concentration of kaolin adsorbed copper was carried on, and the speciation analyses was developed using MINTEQA2. The results of the exposure experiment indicated that expose to kaolin adsorbed copper would increase the metal accumulation in the fish gills. The shift of the copper speciation was demonstrated via chemical equilibrium calculation. To be specific, the kaolin adsorbed copper would be partially desorbed in the fish gill microenvironment in the alkaline water environment.

Intracellular surfactant removal from phagocytized minerals: development of a fluorescent method using a BODIPY-labeled phospholipid.

Lung surfactant serves as a protective coating when adsorbed on particle surfaces, so its removal or rate of removal in vivo may affect expression of mineral cytotoxicity. Removal of phospholipid surfactant components from the surface of mineral particles ingested by alveolar macrophages (AM) was measured using fluorescence microscopy. Dipalmitoylphosphatidylcholine with a fluorescent label (BODIPY(trade mark)) substituted for C1-C4 on the second acyl chain (DPPC*), was mixed with dioleoylphosphatidylcholine (DOPC) to coat respirable quartz and kaolin particles. Fluorescence from quartz or kaolin particles of 3-4, 5-6 and 8-9 microm size decreased in intensity with increasing ratios of DOPC/DPPC* for the same DOPC concentration of 0.4 mg/ml. There was a direct correlation between fluorescence and residual phospholipid surfactant remaining on particles using phospholipase A2 (PLA(2)) digestion in a cell-free system, indicating that the presence of the fluorophore on DPPC did not hinder enzymatic recognition. Lavaged primary AM obtained from male Fischer rats were challenged in vitro with DOPC/DPPC* (10:1 mol:mol) coated particles at 50 microg particles/10(6) cells. In contrast to the biexponential response seen in cell-free experiments, the rate of fluorescence decay from ingested coated quartz or kaolin particles over 7 days was monoexponential, with the same t(1/2) (41 h) for each dust. This study suggests that the rate of phagolysosomal digestion and removal of the adsorbed surfactant is not a determinant of the different mineral-specific pathogenicities or toxicities of quartz and kaolin, although residual fluorescence remained on particles even after 7-8 days.

In vitro adsorption of mebeverine hydrochloride onto kaolin and its relationship to pharmacological effects of the drug in vivo.

The in vitro uptake of mebeverine hydrochloride from an initial drug concentration of 0.25-4.25 or 0.2-3.6 g% w/v onto kaolin 5.0 g% w/v at pH 1.8 or 7.5, respectively, at 37 degrees C was represented by a double- layered adsorption isotherm. The calculated data were in accordance with a Langmuir adsorption isotherm for an initial drug concentration up to 2.1 or 2.0 g% w/v when a monolayer was formed at pH 1.8 or 7.5, respectively. The adsorption process is pH dependent, and is affected by the electrolyte concentration and valency. The amount of the drug desorbed (mg% w/v) by washing with different elution media at 37 degrees C followed the sequence 0.1 M hydrochloric acid > 0.1 M magnesium chloride > 0.1 M sodium chloride > simulated intestinal fluid. The results obtained from this study indicate that two mechanisms, ion exchange and physical adsorption, were involved in the uptake of mebeverine hydrochloride by kaolin. The presence of different concentrations of kaolin with the tablets or capsules of the drug, adversely affected the release rate. The in vivo and in vitro studies on guinea pig ileum showed that the presence of kaolin in a mixture with mebeverine hydrochloride did not affect to any significant level the inhibiting effect of the musculotropic drug on carbachol-induced contractions in the isolated guinea pig ileum. In vivo studies showed similar results for barium chloride as well.

Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters.

Lifetime "nose-only" inhalation studies were conducted in rats using four types of refractory ceramic fibers (FCF), 1 micron in diameter x 22 to 26 microns length: High Purity, Kaolin, Zirconia, and After-Service; and on hamsters using Kaolin RCF. For comparison, animals also were exposed to chrysotile fibers. Rats were exposed 6 hr/day, 5 days/week for 24 months to concentrations ranging between 3 and 30 mg/m3. Time- and dose-dependent lesions in the rat included the development of interstitial fibrosis, pleural fibrosis, pulmonary tumors, and mesothelioma. Exposure to 3, 9 or 16 mg/m3 produced no excess lung tumors; no fibrosis was seen at 3 mg/m3. A significant increase in lung tumors and interstitial fibrosis was observed at 30 mg/m3. A single mesothelioma was observed in rats exposed to 9 mg/m3, while two occurred at 30 mg/m3. Hamsters were similarly exposed to 30 mg/m3 Kaolin RCF for 18 months; no lung tumors were induced, but pulmonary and pleural fibrosis were observed and there was a 42% incidence of mesothelioma. Multiple interim sacrifices together with recovery animals allowed detailed assessment of the lung burden of RCF, which was found to be dose related and, at the high doses, exceeded 10(5) fibers/mg of dry lung. During the various recovery periods there was a clear reduction in fiber burden. Mathematical modeling of these data for deposition, clearance, and retention and for species is currently underway.

Contrasting respirable quartz and kaolin retention of lecithin surfactant and expression of membranolytic activity following phospholipase A2 digestion.

Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral-specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.

[Adsorption potency of 2 clays, smectite and kaolin on bacterial enterotoxins. In vitro study in cell culture and in the intestine of newborn mice]. / Pouvoir d'adsorption de deux argiles, la smectite et le kaolin sur des entérotoxines bactériennes. Etude in vitro sur culture cellulaire et sur intestin de souriceau nouveau-né.

The use of clays in the treatment of enterocolitis is justified by their ability to adsorb viruses, biliary acids and bacterial toxins secreted into the intestinal lumen. We have studied the in vitro inactivation of the LT toxins of Vibrio cholerae and E. coli, the ST toxin of ETEC and the verotoxin of EHEC. These various toxins were incubated with two types of clays, smectite and kaolin, to investigate the influence of dose, pH variations and the duration of contact of the clays with the toxins. Irrespective of their presence or absence in the supernatant, the biological activity of the toxins was assessed in cell culture and in the newborn mouse test. Both clays inactivated the LT toxin. Smectite was more efficient than kaolin as it was active immediately especially at the pH of intestinal chyme. The LT toxins were adsorbed on the clays by hydrogen bonding. This permitted the segregation of the toxins and prevented them from being fixed to the membrane receptors on the cells. The two clays were ineffective against the verotoxin of EHEC when the pH was alkaline although they were more efficient at acid pH. ST toxin of ETEC was slightly adsorbed by smectite and kaolin.