Polymer coated CaAl-layered double hydroxide nanomaterials for potential calcium supplement.

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of pH 1.2. The X-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electron and transmission electron microscopy revealed that the pristine LDH was well prepared having hydrocalumite structure, and that the polymer effectively coated the surface of LDH without disturbing structure. From thermal analysis, it was determined that only a small amount (less than 1%) of polymer was coated on the LDH surface. Metal dissolution from LDH nanomaterials was significantly reduced upon Eudragit®L 100 coating at pH 1.2, 6.8 and 7.4, which simulates gastric, enteric and plasma conditions, respectively, and the dissolution effect was the most suppressed at pH 1.2. The LDH nanomaterials did not exhibit any significant cytotoxicity up to 1000 µg/mL and intracellular calcium concentration significantly increased in LDH-treated human intestinal cells. Pharmacokinetic study demonstrated absorption efficiency of Eudragit®L 100 coated LDH following oral administration to rats. Moreover, the LDH nanomaterials did not cause acute toxic effect in vivo. All the results suggest the great potential of CaAl-LDH nanomaterials as a calcium supplement.

Periodic charge matching driven immobilization of gentamicin in nanoclays for stable and long-term antibacterial coating.

Matching of charge periodicity between a guest and a host enabled effective immobilization of highly water-soluble antibiotic drug, gentamicin C, in a bentonite clay by cation exchange. X-ray diffraction, infrared spectroscopy and CHNS analysis revealed the immobilization manner of gentamicin C, which was immobilized between bentonite layers via periodic charge-charge interaction with tilted arrangement, as a trication. Both gentamicin alone and a gentamicin/bentonite hybrid were coated onto a polyurethane substrate using water-borne polyurethane binder. The antibiotic character of both films was investigated as prepared or after immersion in phosphate-buffered saline till 5 days against E. coli and B. subtilis bacteria. It was clearly shown that the gentamicin/bentonite hybrid-coated film showed sustained antibacterial efficacy even after exposure to phosphate-buffered saline, while gentamicin only-coated film gradually lost its performance under the same condition.

Development of polystyrene coated persulfate slow-release beads for the oxidation of targeted PAHs: Effects of sulfate and chloride ions.

In this study, we synthesized polystyrene coated persulfate polyacrylonitrile beads (PC-PSPANBs) to control persulfate (PS) release for targeted PAHs' degradation in a batch reactor. Initially, the persulfate release rate (ksr = 20.553 h-1) from PSPANBs was fast, but coating the PSPANBs with polystyrene controlled PS release rate (ksr= 2.841 h-1), nearly ten times slower than without coating. When Fe(II) activated PC-PSPANBs applied for 12 h degradation of acenaphthene (ACE), 2-methlynaphthalene (2-MN) and dibenzofuran (DBF), the optimum percent removal efficiencies (% R.Es) were as ACE (82.12%) > DBF (68.57%) > 2-MN (58.80%) and the optimum degradation rate constants (kobs) were found as ACE (11.348 h-1) > 2-MN (3.441 h-1) > DBF (1.101 h-1). The effect of SO42- and Cl- on ACE degradation showed that % R.E and kobs were enhanced with increasing anionic concentrations. The maximum % R.E was achieved for SO42- (76.24%) > Cl- (65.51%), but the highest kobs was in case of Cl- (1.536 h-1) > SO42- (0.510 h-1). The effectiveness of PS release longevity was also found because net degradations of ACE and DBF after first spiking were 12 mg L-1 and 16 mg L-1, while after second spiking were 18 mg L-1 and 10 mg L-1, respectively.

Random array of inorganic nanoparticles on polymer surface for anti-biofouling property through cost-effective and high-performance dip-coating.

Anti-biofouling treatment is required in various fields such as biomedical application, construction, civil engineering, and so on. Currently available techniques such as lithography and replica methods have several limitations in application and accessibility. We introduced a simple, biocompatible, and cost-effective anti-biofouling dip-coating method with polyurethane-inorganic (anisotropic montmorillonite and spherical TiO2) hybrid coating agent. Layer thickness of coating was as thin as 5 µm. It was cross-confirmed with thickness gauge and cross-section scanning electron microscopy. Through atomic force microscopy, inorganic nanoparticles were observed to be randomly arrayed with particles partially embedded in the polyurethane network. The calculated surface roughness of inorganic-polyurethane hybrid coating was five times larger than the neat substrate film and three times larger than coating without inorganic nanoparticles. Surface energy of the inorganic-polyurethane film decreased with increasing surface roughness as random pattern of inorganic particle reduced van der Waals interaction. Biofouling efficacy was evaluated by mucin adsorption and consecutive alcian blue assay. Results showed that coated film decreased biofouling 81% compared to bare film.

Polyethylenimine-functionalized cationic barley ß-glucan derivatives for macrophage RAW264.7 cell-targeted gene delivery systems.

Cationic barley ß-glucan derivatives (bGPEIs) with various polyethylenimine 2k (PEI2k) graft degrees were synthesized by periodate oxidation of backbone vicinal diols and reductive amination of PEI2k for gene delivery systems. bGPEIs could form positively charged (∼40 mV zeta-potential) and nano-sized (∼150 nm) spherical polyplexes. Cytotoxicity of bGPEIs was concentration and PEI graft degree-dependent. bGPEIs showed higher transfection efficiency and intracellular localization ability than PEI25k in RAW264.7 cell, especially in serum condition. High cellular uptake of bGPEI polyplexes at 4 °C in RAW264.7 cells suggested that bGPEIs would possess specific interaction ability with membrane receptors of RAW264.7 cells. In addition, bGPEIs could activate RAW264.7 cells, inducing the secretion of cytokine, tumor necrosis factor-α (TNF-α). Therefore, bGPEIs showed a potential for macrophage RAW264.7 cell-targeted gene delivery systems.

Fe3O4@polypyrrole core-shell nanohybrid for efficient DNA retrieval.

Core-shell nanohybrid, Fe3O4@PPY, which consists of superparamagnetic Fe3O4 core and DNA attractive polypyrrole, was successfully synthesized through the free radical polymerization. The DNA retrieval efficacy of the nanohybrid was found to be very high in DNA solution with low concentration (approximately 33% uptake in 100 microM).

Controlled release of donepezil intercalated in smectite clays.

The inorganic-organic hybrid for a drug delivery system was successfully realized by intercalating donepezil molecules into smectite clays (laponite XLG, saponite, and montmorillonite). According to the powder XRD patterns, TG profiles, and FT-IR spectra, it was confirmed that donepezil molecules were well stabilized in the interlayer space of clay via mono or double layer stacking. The adsorption amount and molecular structure of donepezil appeared to depend on the cation exchange capacity of the clay, which in turn, tailored the drug release patterns. Especially in the presence of a bulky cationic polymer (Eudragit E-100) in the release media, the release rate was found to be improved due to its effective replacement with intercalated donepezil molecules. Therefore, to formulate a complete drug delivery system, the hybrids were coated with Eudragit E-100 using a spray dryer, which also showed great enhancement in the release rate during a short period of time (180min).

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO3) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO3 is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO3 in comparison with that of bulk- or reagent grade nano CaCO3 in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO3 particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO3 nanoparticles were different from bulk CaCO3 or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO3 nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO3 particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.

Layered double hydroxide as an efficient drug reservoir for folate derivatives.

Folic acid derivatives such as folinic acid and methotrexate (MTX) have been successfully hybridized with layered double hydroxide (LDH) by ion-exchange reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that these molecules intercalated into the hydroxide interlayer space are stabilized in the tilted longitudinal monolayer mode by electrostatic interaction. No significant changes in their structural and functional properties are found in the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The initial proliferation of SaOS-2 cell is more strongly suppressed by treatment with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not only plays a role as a biocompatible-delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency.

Insulin-loaded microcapsules for in vivo delivery.

Microencapsulation of insulin has been difficult, due to the high sensitivity of insulin to the harsh conditions that can occur during the microencapsulation process. We have developed a method of preparing insulin-loaded microcapsules by using a monoaxial ultrasonic atomizer to form microdroplets of insulin in aqueous solution surrounded by poly(lactic-co-glycolic acid) (PLGA) solution. Administration of these insulin-loaded microcapsules to type 1 diabetic rats maintained plasma insulin concentrations for 30 days, due to the sustained insulin release properties of the microcapsules. In contrast, plasma insulin concentrations after subcutaneous injection of insulin solution reached near zero levels within 2 days. Insulin solution showed only an immediate pharmacological effect, with no reduction of glycemia after 3 days, whereas insulin-loaded microcapsules maintained blood glucose levels at 100-200 mg/dL for 55 days. Molecular imaging using fluorescein isothiocyanate (FITC)-insulin-loaded microcapsules showed in vivo sustained release of the FITC-insulin in microcapsules. Using insulin-loaded microcapsules, we observed inflammation only immediately after injection, indicating that the rats adapted to long-term insulin release. In conclusion, insulin-loaded microcapsules may reduce nonrepetitive insulin administration and show sustained pharmacological performance.