Hyperbranched Double Hydrophilic Block Copolymer Micelles of Poly(ethylene oxide) and Polyglycerol for pH-Responsive Drug Delivery

Abstract

We report the synthesis of a well-defined hyperbranched double hydrophilic block copolymer of poly(ethylene oxide)-hyperbranched-polyglycerol (PEO-hb-PG) to develop an efficient drug delivery system. In specific, we demonstrate the hyperbranched PEO-hb-PG can form a self-assembled micellar structure on conjugation with the hydrophobic anticancer agent doxorubicin, which is linked to the polymer by pH-sensitive hydrazone bonds, resulting in a pH-responsive controlled release of doxorubicin. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy demonstrated successful formation of the spherical core-shell type micelles with an average size of about 200 nm. Moreover, the pH-responsive release of doxorubicin and in vitro cytotoxicity studies revealed the controlled stimuli-responsive drug delivery system desirable for enhanced efficiency. Benefiting from many desirable features of hyperbranched double hydrophilic block copolymers such as enhanced biocompatibility, increased water solubility, and drug loading efficiency as well as improved clearance of the polymer after drug release, we believe that double hydrophilic block copolymer will provide a versatile platform to develop excellent drug delivery systems for effective treatment of cancer.

Stimuli-responsive copolymer solution and surface assemblies for biomedical applications

“…For example, Lee et al assembled micelles from a double-hydrophilic hyperbranched copolymer, poly(ethylene glycol- hb -glycerol) (PEG- hb -PG), in which the anti-cancer drug doxorubicin was conjugated to the hyperbranched PG units via acid-labile hydrazone linkages. 25 Attachment of the hydrophobic drug rendered the PG segments hydrophobic, and the resulting amphiphilic copolymer formed micelles in aqueous solutions. Upon cleavage of the hydrazone linkage in solution at pH = 5.0, or in the endolysosomal compartments within human cervical cancer HeLa cells, doxorubicin was released, and the micelles disassembled into relatively benign PEG- hb -PG unimers.…”

Responsive hybrid (poly)peptide–polymer conjugates

“…43 Within the past decade there has been a push to advance beyond PEGylation, as recent literature has documented anti-PEG antibodies that have a detrimental effect on drug efficacy. 44 A range of PEG-alternatives such as poly(N-vinylpyrrolidone), 45 poly(glycerol), 46 poly(zwitterions), 47 poly(carbonates), 48 poly(oxazolines), 49 and poly(sacharrides), 50 have shown promise, and have been reviewed elsewhere. 51,52 In addition, polyphosphoesters (PPE) represent an important alternative to PEG because of their biocompatibility, biodegradability, similar architecture to biomolecules, and ability to be functionalized.…”

Chitosan-Based Thermosensitive Materials

“…Cs-GP system has a great potential as scaffold material in tissue engineering and regenerative medicine due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the possibility to be moulded in various geometries [18][19][20][21][22][23][24][25][26]. For similar reasons, the other key pharmaceutical application of this material is a smart-controlled release system [4,18,20,[27][28][29][30][31][32][33][34][35][36][37][38], because the hydrogel is able to keep the drug level within the therapeutic window during extended periods of time, thus avoiding frequent low doses and undesirable secondary effects in patients. Important and interesting patents of biomedical applications of this system have been revised recently [39].…”