Solubilization and formulation of chrysosplenol C in solid dispersion with hydrophilic carriers.

We investigated how to overcome problems associated with the solubility, dissolution, and oral bioavailability of the poorly water-soluble drug compound, chrysosplenol C (CRSP), as well as the effects of single and binary hydrophilic polymers (PVP K-25 and/or PEG 6000) on the solubility and dissolution parameters of CRSP. Then an optimized formulation was further developed with a surfactant. To select a surfactant suitable for a CRSP-loaded solid dispersion (SD), the solubility of CRSP in distilled water containing 1% surfactant was compared with the solubilities in other surfactants. Sodium lauryl sulfate (SLS) showed the highest drug solubility. Overall, a formulation containing CRSP, binary hydrophilic polymers (PVP and PEG 6000), and SLS at a ratio of 2.0/0.2/1.1/0.7 showed the optimum in vitro release profile. This optimized formulation had better safety properties than pure CRSP in cell viability examinations. SD formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy. Our optimized SD formulation is expected to improve the bioavailability of CRPS because it improves the solubility and dissolution rate of CRSP.

Combined delivery of the adiponectin gene and rosiglitazone using cationic lipid emulsions.

For the combined delivery of an insulin-sensitizing adipokine; i.e., the ADN gene, and the potent PPARγ agonist rosiglitazone, cationic lipid emulsions were formulated using the cationic lipid DOTAP, helper lipid DOPE, castor oil, Tween 20 and Tween 80. The effect of drug loading on the physicochemical characteristics of the cationic emulsion/DNA complexes was investigated. Complex formation between the cationic emulsion and negatively charged plasmid DNA was confirmed and protection from DNase was observed. The in vitro transfection efficiency and cytotoxicity were evaluated in HepG2 cells. The particle sizes of the cationic emulsion/DNA complex were in the range 230-540 nm and those of the rosiglitazone-loaded cationic emulsion/DNA complex were in the range 220-340 nm. Gel retardation of the complexes was observed when the complexation weight ratios of the cationic lipid to plasmid DNA exceeded 4:1 for both the drug-free and rosiglitazone-loaded complexes. Both complexes stabilized plasmid DNA against DNase. The ADN expression level increased dose-dependently when cells were transfected with the cationic emulsion/DNA complexes. The rosiglitazone-loaded cationic emulsion/DNA complexes showed higher cellular uptake in HepG2 cells depending on the rosiglitazone loading, but not depending on the type of plasmid DNA type such as pVAX/ADN, pCAG/ADN, or pVAX. The drug-loaded cationic emulsion/plasmid DNA complexes were less cytotoxic than free rosiglitazone. Therefore, a cationic emulsion could potentially serve as a co-delivery system for rosiglitazone and the adiponectin gene.

Exploring the Preparation of Albendazole-Loaded Chitosan-Tripolyphosphate Nanoparticles.

The objective of this study was to improve the solubility of albendazole and optimize the preparation of an oral nanoparticle formulation, using ß-cyclodextrin (ßCD) and chitosan-tripolyphosphate (TPP) nanoparticles. The solubility of albendazole in buffers, surfactants, and various concentrations of acetic acid solution was investigated. To determine drug loading, the cytotoxic effects of the albendazole concentration in human hepatocellular carcinoma cells (HepG2) were investigated. The formulations were prepared by mixing the drug solution in Tween 20 with the chitosan solution. TPP solution was added dropwise with sonication to produce a nanoparticle through ionic crosslinking. Then the particle size, polydispersity index, and zeta potential of the nanoparticles were investigated to obtain an optimal composition. The solubility of albendazole was greater in pH 2 buffer, Tween 20, and ßCD depending on the concentration of acetic acid. Drug loading was determined as 100 µg/mL based on the results of cell viability. The optimized ratio of Tween 20, chitosan/hydroxypropyl ßCD, and TPP was 2:5:1, which resulted in smaller particle size and proper zeta positive values of the zeta potential. The chitosan-TPP nanoparticles increased the drug solubility and had a small particle size with homogeneity in formulating albendazole as a potential anticancer agent.

Thermosensitive and mucoadhesive sol-gel composites of paclitaxel/dimethyl-ß-cyclodextrin for buccal delivery.

The purpose of this study was to develop a buccal paclitaxel delivery system using the thermosensitive polymer Pluronic F127 (PF127) and the mucoadhesive polymer polyethylene oxide (PEO). The anticancer agent paclitaxel is usually used to treat ovarian, breast, and non-small-cell lung cancer. To improve its aqueous solubility, paclitaxel was incorporated into an inclusion complex with (2,6-di-O-methyl)-ß-cyclodextrin (DMßCD). The formation of the paclitaxel inclusion complex was evaluated using various techniques, including x-ray diffractometry (XRD), Fourier-transform infrared (FT-IR) spectrophotometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Hydrogels were prepared using a cold method. Concentrations of 18, 20, and 23% (w/v) PF127 were dissolved in distilled water including paclitaxel and stored overnight in a refrigerator at 4 °C. PEO was added at concentrations of 0.1, 0.2, 0.4, 0.8, and 1% (w/v). Each formulation included paclitaxel (0.5 mg/mL). The sol-gel transition temperature of the hydrogels was measured using the tube-inverting method. Drug release from the hydrogels was measured using a Franz diffusion cell containing pH 7.4 phosphate-buffered solution (PBS) buffer at 37 °C. The cytotoxicity of each formulation was measured using the MTT assay with a human oral cancer cell (KB cell). The sol-gel transition temperature of the hydrogel decreased when PF127 was present and varied according to the presence of mucoadhesive polymers. The in vitro release was sustained and the release rate was slowed by the addition of the mucoadhesive polymer. The cytotoxicity of the blank formulation was low, although the drug-loaded hydrogel showed acceptable cytotoxicity. The results of our study suggest that the combination of a PF 127-based mucoadhesive hydrogel formulation and inclusion complexes improves the in vitro release and cytotoxic effect of paclitaxel.