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.
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.
Chen
Yi
Y
Department of Polymer Science & Engineering, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, PR China.
Dong
Chang-Ming
CM
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D004318:Doxycycline / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006016:Glycolates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid; D008422:Materials Testing; D008823:Micelles; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D006016:Glycolates; D008823:Micelles; D010455:Peptides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004318:Doxycycline