| Nowadays, phosphatidylcholine mixed micelles have been widely used to improve the solubility of insoluble drugs and food active ingredients to enhance its bioavailability, but a few mixed micellar drug products were used in the commercial pharmaceutical and food industry. Previous studies concentrated on the phosphatidylcholine/ionic surfactant mixed micelle system, however, only several ionic surfactants can be used in a limited range. Therefore, in order to meet the large market demand, it is necessary to develop a novel phosphatidylcholine mixed micelles system.The soya phosphatidylcholine (SPC) and nonionic surfactants which were hydrophilic and low toxic were selected as raw materials, the micelles systems were evaluated by light transmittance, particle size and size distribution. It was shown that the shorter chain length of the surfactant's hydrophobic aliphatic was, the stronger the effect of the surfactant on solubilization of phosphatidylcholine had. Besides, decaglycerol laurate (L-7D) was chosen as the optimum surfactant. Among those surfactants, L-7D was of good biocompatibility, and it didn't cause hemolysis, what's more, it had strong effect on improving solubilization of phosphatidylcholine and it was able to form clear solutions with soya phosphatidylcholine at a higher ratio in a wide range of concentrations, as well as showing a unimodal particle size distribution. Thus, a good application prospect was forecasted for L-7D.The SPC and L-7D were mixed as compound objects, the optimum preparation parameters of the direct dispersion method were chosen by singer factor experiments and orthogonal experiments: the mass ratio of SPC to L-7D was 1:2, the hydration temperature was 70℃, the hydration time was 4 h, the emulsion shear speed was 22000 r/min and the emulsion shear time was 6 min. Under the conditions, the light transmittance of the mixed micelles was 99.1±0.92%, and the average particle size was 10.25±0.86 nm. The mixed micelles systems prepared by the direct dispersion method and the traditional film-forming or the evaporation method respectively were compared under the same formula. It was suggested that the quality of the micelles system prepared by direct dispersion method was equivalent to the film forming method. Meanwhile,there was no organic solvent residue.In the present study, to investigate the properties of SPC/L-7D mixed micelles system, the CMC of different ratios of the systerms were determined by the surface tension method. It was indicated that as SPC mass concentration increased, the CMC of the mixed micelles system decreased. It was also suggested that the addition of SPC played a very important role in the stability of the mixed micelles, and enhanced the kernel hydrophobicity of the mixed micellars. By pyrene fluorescence probe method, it was shown that the micro-polarity in the mixed micelles decreased as the concentration of SPC increased. However, the non-polar of the environment where pyrene located was strengthened, and the quantity of aggregated mixed micelles also increased as the concentration of the total surfactant increased. By dynamic scattering method and transmission electron microscopy technology, with the increase of the concentration of phospholipids in the system, the aggregation changed from the single particle micelles to mix micelles, then to big particle phospholipids vesicles. To inhibit the production of lysophospholipids (LPC),the relative content of LPC to SPC in the mixed micelles system had been determined by HPLC-ELSD. The results showed that the production of LPC can be effectively inhibited under the condition of low storage temperature and light intensity, high concentration of electrolyte and alkaline environment. The experiments of integrated storage and centrifugal stability showed that the particle sizes, PDI value, light transmittance and Ke had not changed much. In conclusion, the mixed micelles system was stable in this study. |
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