Abstract
A novel mixed micelles composed of methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PLA) and methoxy poly(ethylene glycol)-b-poly(N-n-propylacrylamide-co-vinylimidazole) (mPEG-b-P(Nn-PAAm-co-VIm)) diblock copolymers, having critical micelle concentration (CMC) and critical micelle temperature (CMT) properties, were successful prepared in this study. Such nanostructures have well biocompatibility and thermal/pH sensitivity owing to their component natures. Based on these advantages, mixed micelles had a candidate as drug carriers for cancer therapy.The thermal/pH responsive properties of mixed micelles can be measured by UV/vis spectrometer at 542 nm. The lower critical solution temperature (LCST) occurred at 21.5℃~35℃ and gradually increased with reducing environment pH, and therefore we utilized its special behavior to prepare well-mixed micelles that exhibited a uniform size about 75~100nm and narrow polydispersity about 0.1~0.2 under 37℃ buffer solution via hot-shock protocol. Furthermore, the use of pyrene as probe for fluorescence spectroscopic measurement could observe that the I1/I3 decreased with raising surrounding temperature, indicating that the probe diffused from aqueous phase to the core of mixed micelles.The characteristics and morphologies of mixed micelles were analyzed from 1H-NMR, DLS, zeta potential, fluorescence spectrometer, AFM, and TEM. Additionally, doxorubicin (Dox) was incorporated into mixed micelles for cancer therapy. In neutral surroundings, the release of Dox from mixed micelles was less. In contrast, a significant release of Dox was observed in acidic surroundings about pH＜6. The amount of drug released from mix micelles was isolated from mixed micelles buffer solution by ultrafiltration and measured by UV/vis spectrometer at 485 nm in a time-course procedure.The result of CLSM observation indicated the loading drug successfully released in the acidic organelles due to the deformation of the micelle structure.Above all, the release of drug from mixed micelles could be strongly controlled by pH changes. From these results, the novel mixed micelles showed high potential for drug carriers in intracellular drug delivery.