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The objective of this study was to prepare a fenofibrate-loaded emulsion. The emulsion was formulated by mixing olive oil, surfactants (mixture of Tween 20 and Tween 80), and distilled water. To find the emulsion composition, the phase diagram was investigated based on the mixture of olive oil, surfactants, and distilled water. From the phase diagram, one-phase formulations were selected and particle sizes of those formulations were compared. Stability was confirmed for 4 weeks at 4 °C based on the change in particle size. The effect of dilution on the pH of the emulsion formulations was observed. The concentration of olive oil was 5 %, enough to obtain a small-sized emulsion. The surfactants were used as a mixture of Tween 20 and Tween 80 in a 1:2 ratio to show high solubility of fenofibrate. Three formulations, termed E1, E2, and E3, showed relatively small-sized emulsion. The fenofibrate-loaded E2 formulations showed smaller particle sizes than other formulations. The three formulations were physically stable for 4 weeks with no significant change in particle size. Dilution with distilled water did not alter the pH of the three emulsion formulations, but changed the conductivity. In conclusion, fenofibrate was solubilized by the emulsion formulation, the stability of the emulsion formulation was maintained at 4 °C, and the pH of formulation was not altered, but the conductivity of formulation was changed by dilution with distilled water.

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.

The objective of this study was to improve the solubility of albendazole and optimize the preparation of an oral nanoparticle formulation, using beta-cyclodextrin (beta CD) 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 beta CD depending on the concentration of acetic acid. Drug loading was determined as 100 mu g/mL based on the results of cell viability. The optimized ratio of Tween 20, chitosan/hydroxypropyl beta CD, 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.

Albendazole is poorly soluble in water and has low bioavailability. The objective of this study was to improve the solubility of albendazole and optimize preparation of an oral nanoparticle formulation, using chitosan-tripolyphosphate (TPP) nanoparticles. The formulation was prepared by mixing the drug solution in Tween 20 with the chitosan solution. TPP solution was added drop wise with sonication to produce a nanoparticle through ionic crosslinking. The dispersion method and TPP loading devices were varied to prepare desirable-sized nanoparticles and subsequently examine drug solubility, nanoparticle size and cytotoxicity. Cytotoxicity of each vehicle was measured by MTT assay. The particle size of blank nanoparticles was 370 nm with a 0.171 polydispersity index when the volume ratio of TPP to chitosan was 1:5. Addition of Tween 20 to solubilize albendazole increased particle size and polydispersity index to 470 nm and 0.251, respectively. The optimized preparation conditions were water bath sonication for 30 min and TPP loading using yellow pipette tips, which produced a small particle size of 235 nm and a polydispersity index of 0.367. Filtration reduced particle size, but increased the polydispersity index. The albendazole-loaded nanoparticles showed higher cytotoxicity than albendazole suspension, even though the chitosan-TPP nanoparticle formulation was itself not toxic. The chitosan-TPP nanoparticles increased the drug solubility and have the potential to deliver albendazole as an anti-cancer agent.

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.

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)-beta-cyclodextrin (DM beta CD). 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 degrees 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 degrees 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.