pH-sensitive supramolecular polypeptide-based micelles and reverse micelles mediated by hydrogen-bonding interactions or host-guest chemistry: characterization and in vitro controlled drug release.J Phys Chem B 2010; 114(22):7461-8JP
A versatile strategy is provided for the fabrication of pH-sensitive polypeptide-based normal micelles and reverse micelles from the same polypeptide-based copolymers via hydrogen-bonding interactions or host-guest chemistry. The pH-sensitive self-assembly of both linear and dendron-like/linear poly(L-glutamic acid)-b-poly(ethylene oxide) (Dm-PLG-b-PEO) block copolymers was investigated in detail by means of UV-vis, dynamic light scattering, NMR, fluorescence spectroscopy, and transmission electron microscopy. It was demonstrated that both the copolymer topology and the composition controlled the morphology of the polypeptide-cored normal micelles. Importantly, a novel class of polypeptide-shelled reverse micelles was for the first time generated by host-guest-chemistry-mediated self-assembly of these copolymers and alpha-cyclodextrin (alpha-CD) in alkaline solution. The supramolecular inclusion complexation between PEO and alpha-CD was confirmed by wide-angle X-ray diffraction, differential scanning calorimetry, and NMR. Moreover, the zeta potential of the reverse micelles ranged from -20.2 to -24.2 mV, convincingly demonstrating that the reverse micelles had an anionic PLG shell. Furthermore, the anticancer doxorubicin (DOX)-loaded micelles fabricated from the dendron-like/linear copolymer showed a higher DOX loading efficiency (38%) and capacity (24%) and sustained a longer drug-release period (approximately 70 days) than the linear counterpart. Consequently, this will provide a platform for the fabrication of supramolecular polypeptide-cored and polypeptide-shelled micelles for the anticancer drug delivery systems.