Novel Biomimetic Mixed Micelle Based On MePEG-Chol And MePEG-St For Drug Delivery

Novel biomimetic mixed micelles based on Methoxy poly(ethylene glycol)-cholesterol (MePEG-Chol) and Methoxy poly(ethylene glycol)-stearic acid (MePEG-St) as amphiphilic polymer conjugates were prepared in the present study. MePEG-Chol conjugate was synthesized under mild conditions by reacting carboxylic acid-terminated cholesterol with hydroxyl-terminated PEG in the presence of dicyclohexylcarbodiimide (DCC) and DMAP. The MePEG-St conjugate was prepared by conjugating carboxylic acid of stearic acid and hydroxyl-terminated PEG using DCC as a coupling agent. Synthesized MePEG-Chol and MePEG-St were confirmed by Fourier transform-infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. Mixed micelles with different molar ratio of the two conjugates were produced by a precipitation method. The critical micelle concentration (CMC) of mixed micelle determined by surface tension measurement and fluorescence spectroscopy was lower than that of the common low molecular weight surfactant. The size of nanospheres measured by dynamic light scattering (DLS) showed the average diameter about 10 nm and a narrow monodisperse size distribution. From the observation of transmission electron microscopy (TEM), the mixed micelle exhibited a spherical shape and the structure was considered to be similar to cell membrane. This constructed biomimetic mixed micelle can be used for the delivery of hydrophobic drugs. In order to investigate the drug release behavior, indomethacin (IMC) was chosen as a hydrophobic drug to be incorporated into the inner core of the mixed micelle. The release rate of IMC from the mixed micelle was slow and continued about 6 days. The results showed that the mixed micelle was formed and the stability of micelle was better in mixed systems than that in neat MePEG-Chol or MePEG-St system. This phenomenon was the same as that cholesterol regulated membrane fluidity and played an important role in stability as one of the most common membrane sterols in animals.