Development of raft-forming liquid formulations loaded with ginger extract-solid dispersion for treatment of gastric ulceration.

Raft-forming liquid formulations incorporating ginger extract solid dispersion (GE-SD) were developed to achieve prolonged delivery of 6-gingerol in the stomach and thus increase the effectiveness of gastric ulcer treatment. The solubility of 6-gingerol in 0.1 N HCl (pH 1.2) was maximized (15 mg/mL) by combining ginger extract with PVP K30 at 1:3 w/w ratio to produce a solid dispersion. The nature of GE-SD was confirmed by PXRD and FT-IR analysis. PXRD pattern showed miscibility of GE and PVP K30 in amorphous solid dispersion and the FT-IR spectra confirmed the formation of hydrogen bond between GE and PVP K30. GE-SD-loaded raft-forming liquids were prepared using sodium alginate as a gel former and HPMC as a release-controlling agent. The formulations exhibited rapid floating behavior in 0.1 N HCl (<30 s) and remained afloat on the surface over 8 h. The formed raft structures provided sufficient strength (>7.5 g) and allowed sustained release of more than 70 % of the 6-gingerol content over 8 h in 0.1 N HCl. Raft-forming formulations incorporating ginger extract demonstrated anti-inflammatory activity by inhibiting nitric oxide production in LPS-stimulated RAW 264.7 macrophage cells (IC50 = 5.13 ± 0.07 µg/mL). Exposure to the formulations also had a significant cytotoxic effect on AGS human gastric adenocarcinoma cells with an IC50 of 17.45 ± 0.29 µg/mL. In addition, the raft-forming formulations enhanced the migratory behavior of L929 mouse fibroblasts in the scratch wound model. Taken together, these findings reveal the benefits of gastro-retentive, GE-SD-loaded raft-forming liquid formulations for improving the treatment of gastric ulcers.

Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis.

Novel hydrogels were prepared by blending 4% (w/w) methylcellulose (MC) with various concentrations of 12, 14, 16, 18 and 20% (w/w) pluronic F127 (PF) to form injectable implant drug delivery systems. The blends formed gels using lower concentrations of PF compared to when using PF alone. Etidronate sodium (EDS) at a concentration of 4×10(-3)M was loaded into these blends for producing an osteogenesis effect. The pure gels or EDS loaded gels exhibited cytocompatibility to both the osteoblast (MC3T3-E1) and myoblast (C2C12) cell lines whereas the gels of 16PF, 18PF and 20PF were very cytotoxic to the cells. The EDS loaded gels demonstrated significantly greater alkaline phosphatase (ALP) activities compared to the pure gels. The longer exposure time periods of the samples to the cells, the greater was the ALP activity. These EDS loaded gels significantly increased proliferation of both cell lines thus indicating a bone regeneration effect. The PF/MC blends prolonged the in vitro release of EDS for more than 28 days. Based on the in vitro degradation test, the MC extensively improved the gel strength of the PF and delayed the degradation of the gels thus making them more functional for a sustained drug delivery for osteogenesis.

The efficacy of hydroxyapatite composite impregnated with amphotericin B.

We investigated the efficacy of local biodegradable composites composed of hydroxyapatite-plaster of paris and either chitosan or alginate binder impregnated with amphotericin B. Antifungal activity was tested for Candida albicans using a modified disc diffusion technique for 6 weeks and compared with similarly impregnated polymethylmethacrylate. The physicochemical properties of each preparation were evaluated using scanning electron microscopy and Fourier transform infrared spectroscopy. The antifungal activity of amphotericin B eluted from the hydroxyapatite composites was significantly greater than the polymethylmethacrylate after 7 days. The hydroxyapatite composites and the polymethylmethacrylate system sustained their antifungal activity for at least 1 month. However, after 5 weeks, the antifungal activities of the polymethylmethacrylate systems rapidly lessened, while the hydroxyapatite composites sustained their activities at a much higher level. We found no difference in antifungal activity between the hydroxyapatite composite using either the chitosan or alginate binder. Scanning electron microscopy and Fourier transform infrared spectroscopy revealed the drug release profile. The hydroxyapatite composites impregnated with amphotericin B showed superior antifungal efficacy over those loaded in polymethylmethacrylate in an in vitro study, but additional in vivo research is needed to confirm this result.

The use of chitosan as a condensing agent to enhance emulsion-mediated gene transfer.

Previously we have formulated a new cationic emulsion, composed of 3beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol and dioleoylphosphatidyl ethanolamine, castor oil and Tween 80, and it efficiently delivered plasmid DNA into various cancer cells with low toxicity. Chitosan is a natural cationic polysaccharide and is able to form polyelectrolyte complexes with DNA, in which the DNA is condensed and protected against nuclease degradation. Based on these facts, chitosan was used as a condensing agent to enhance the transfection efficiency of cationic emulsion-mediated gene delivery vehicle. The particle size, zeta potential and transmission electron micrographs of DNA/emulsion complexes were observed before and after condensation by chitosan. In vitro transfection efficiency of naked or precondensed DNA/emulsion (pcDNA/E) complexes was investigated in human hepatoma cells (HepG2) using flow cytometer, confocal microscope and western blot. In addition, in vivo gene transfer was also evaluated as GFP mRNA expression by reverse transcriptase-polymerase chain reaction. The size of transfection complexes was reduced after the condensation of DNA by chitosan. Moreover, when the pcDNA/E complexes were administered into the mice, the GFP mRNA expression was prolonged in liver and lung until day 6. These results suggest that the use of chitosan enhance the in vitro transfection efficiency and extend in vivo gene transfer.

The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery system.

Local biodegradable carriers have been studied for use as a skeletal drug delivery system. This study investigated the efficacy of a local biodegradable composite composed of hydroxyapatite, plaster of Paris, and chitosan impregnated with antibiotics to treat methicillin-resistant Staphylococcus aureus. The composite, impregnated with vancomycin, fosfomycin, or sodium fusidate was tested for its sustained elution characteristics during 3 months and compared with similarly impregnated polymethylmethacrylate using the modified disc diffusion technique. Physicochemical properties using scanning electron microscopy and xray diffraction analysis of each preparation also were analyzed. Vancomycin and fosfomycin incorporated into the hydroxyapatite composite inhibited the organism for 3 months, whereas sodium fusidate was effective only for 3 weeks. Vancomycin and fosfomycin loaded into the hydroxyapatite composite had a significantly better inhibitive effect than when loaded in polymethylmethacrylate, whereas sodium fusidate loaded in polymethylmethacrylate showed a significantly better inhibitive effect than when loaded in the hydroxyapatite composite. Scanning electron microscopy and xray diffraction analysis elucidated the patterns of each drug release profile. The local hydroxyapatite composite is a promising local biodegradable delivery system for vancomycin and fosfomycin, whereas PMMA is a better carrier for sodium fusidate in treating methicillin-resistant staphylococcus aureus osteomyelitis.