The characterisitics of temperature/pH sensitive block copolymer micelles in vitro

The dialysis method was employed to prepare blank and doxorubicin (DOX) loaded micelles formed by temperature- and pH- sensitive polyhistidine-co-polyDL-lactide-co-glycolide-co-polyethyleneglycol- co-polyDL-lactide-co-glycolide-co-polyhistidine (PHis-b-PLGA-b-PEG-b-PLGA-b-PHis).  The critical micelle concentrations (CMC) of the copolymers were measured with Pyrene Fluorescent Probe Technique.  The temperature- and pH- sensitive properties of the blank micelles solution were investigated by optical transmittance measurement.  The morphology and diameter of DOX micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS).  The entrapment rate and drug-loading rate were determined with dialysis method.  The in vitro release study was further performed to examine the temperature- and pH-responsive drug release behavior from DOX-loaded micelles.  The results indicated that the CMC, entrapment efficiency and drug-loaded amount of the micelles were 7.5 × 10^{−3 g·L−1}, 85.2 ± 3.1% and 10.4 ± 4.5%, respectively.  The DOX micelle was globular-shaped with a mean diameter of 91.1 ± 15.8 nm.  The transmittance of micelle solution consistently increased with the increasing temperature or decreasing pH.  In comparison to the drug release profile at physiological conditions (37 ℃, pH 7.4), the DOX-loaded micelles showed faster drug release rate at higher temperature (41 ℃), lower pH (pH 7.0, pH 6.5, pH 5.0) or higher temperature and lower pH (41 ℃, pH 5.0).  This indicated that the micelles showed a temperature and pH-triggered drug release pattern.  Base on the above results, it can be concluded that PHis-b-PLGA-b-PEG-b-PLGA-b-PHis block copolymer micelles which respond to temperature and pH stimuli are promising smart carriers for anti-tumor drugs with the advantages of temperature- and pH- triggered drug release.