ABSTRACT
In this study, artemether (ARM)-loaded mixed micelles (MM) composed of the sodium glycocholate (SGC) and soybean lecithin (SL) were prepared by film dispersion method. The effects of hydration medium, SL mass ratio and total concentration of excipients on the solubilization of ARM were investigated and the stability of MM was evaluated. Results showed that the particle size distribution of SGC-SL-MM prepared by phosphate buffer solution (PBS, pH 7.4, 0.05 mol·L-1) was uniform, with an average size of 3.58 ± 0.14 nm and the polydispersity index (PDI) value was 0.16 ± 0.04. The solubility of ARM increased significantly from 0.64 ± 0.04 mg·mL-1 to 13.7 ± 0.13 mg·mL-1 along with the concentration of total excipient increasing from 1.0% to 30.0% (w/w). The calculated results of Arrhenius parameter and storage stability showed that the degradation rate constant of ARM in MM was smaller than that in acetonitrile-PBS (pH 7.4) at either 37 ℃ or 60 ℃. The experimental ARM-MM was clear after storing for two months at 25 ℃ and the degradation of ARM was less than 7.0%. In conclusion, the SGC-SL-MM can not only improve the solubility of ARM in aqueous solution, but also improve its chemical stability in aqueous solution at low temperature.
ABSTRACT
Melanoma is a malignant tumor with a high degree of malignancy. The incidence of melanoma keeps increasing annually. In this study, a melanoma targeted hyaluronic acid (HA) nanogel was synthesized via crosslinking of thiolated HA with terminally functionalized F127-TPGS mixed micelles. Its stability in vitro was evaluated by the average particle size, and the cytotoxicity of the nanogel was investigated by in vitro cell based assays. Next, cell uptake studies were performed to quantitatively and qualitatively investigate the uptake of the nanogels in B16F10 cells. A small sized nanogel with a diameter of 30 nm was synthesized, which was proven to be minimally cytotoxic against both 3T3 or B16F10 cells. Compared with 3T3 cells with low levels of CD44, B16F10 cells with high levels of CD44 showed significantly higher cell uptake efficiency (P<0.05).
ABSTRACT
OBJECTIVE: To prepare luteolin-loaded Solutol hsl5/Poloxamerl88 mixed micelles, evaluate their pharmaceutical property and study their anti-tumor activity. METHODS: The luteolin-loaded mixed micelles were prepared by thin-film hydration method. The particle size was measured by laser granulometry, and the morphology was observed under transmission electron microscope (TEM). The in vitro release behavior was determined by the dialysis method. Cell toxicity and uptake assays were employed to evaluate the anti-tumor activity. The targeting effect was studied by fluorescence labeling. RESULTS: The prepared luteolin-loaded mixed micelles showed spherical and regular shape with an average particle size of 66.43 nm and its entrapment efficiency was more than 80%. The 12 h-accumulated release ratio in vitro was up to 97.42%. The cytotoxicity of luteolin-loaded mixed micelles on human lung adenocarcinoma cell line A549 was significantly stronger than that of free luteolin and the uptake rate was improved. After injecting DiR-loaded mixed micelles into nude mouse, the drug begun to accumulate in tumors after 2 h and reached the highest concentration at 6 h which was significantly higher than that in other tissues. There remained strong drug distribution in the tumors after 12 h. CONCLUSION: The Solutol hs15/Poloxamer188 mixed micelles have small particle size and high entrapment efficiency and can enhance cell toxicity and uptake with certain passive targeting effect. It is a promising delivery system for anti-tumor drug.
ABSTRACT
OBJECTIVE: To improve the oral bioavailability of glycyrrhizin by preparing glyeyrrhizin-sodium deoxycholate/phos-pholipid-mixed micelles (GL-SDC/PL-MMs). METHODS: GL-SDC/PL-MMs was prepared by a film dispersion method. In order toevaluate the property GL-SDC/PL-MMs comprehensively, physical and chemical properties determination, in situ intestinal absorption, and pharmacokinetics test were carried out. RESULTS: The average particle size of drug-loaded micelles prepared by film dispersion method was (82.99±7.5) nm and Zeta potential was (-32.23±1.05) mV. Compared with the control drug, glycyrrhizin loaded in SDC/PL-MMs significantly improved its in situ intestinal absorption. The oral bioavailability was markedly enhanced, indicated by the increase of ρmax to 77.26 μg · mL-1, which was 2.82 times of that of the control drug. CONCLUSION: SDC/PL-MMs is expected to be developed into a new drug delivery systems of GL.
ABSTRACT
OBJECTIVE: To study the oral absorption of paclitaxel-loaded mixed micelles made of D-α-tocopherol polyethylene glycol 1000 succinate(TPGS) and sodium cholate(NaC) in rats. METHODS: Paclitaxel-loaded mixed micelles were prepared by film dispersion method. The Zeta potential and diameter distribution of TPGS/NaC mixed micelles were measured using laser size scattering determinator. The morphology of micelles was observed by transmission electron microscope. Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro. The absorption kinetics was obtained by in situ perfusion method in rats. RESULTS: Most of the mixed micelles were spherical with an average diameter of 24.2 nm and the Zeta potential was -7.84 mV. Compared to the bulk drug, the apparent absorption rate constant (Ka)of paclitaxel-loaded mixed micelles was increased significantly. CONCLUSION: TPGS/NaC mixed micelles can improve the oral absorption of paclitaxel and increase its oral bioavailability.