Preparation of glycoside polymer micelles with antioxidant polyphenolic cores using alkylated poly(arbutin)s.

This paper describes the synthesis of long-chain-alkylated poly(arbutin)s (poly(Arb)-R x , where R = alkyl-chain length and x = degree of substitution (DS)) and their aqueous micelle formation. DS was controlled by tailoring the alkyl reagent/main-chain phenol substituent feed ratio. The critical micelle concentrations (CMCs) of poly(Arb)-R x were determined as 1.3-5.2 mg mL-1 by the surface tension method. Introduction of longer alkyl substituents decreased CMC and also decreased aqueous solubility. In DLS measurement, the average micelle diameters were 225-616 nm, and micelle size decreased with increasing DS because of increased stabilization by hydrophobic alkyl substituents. Transmission electron microscopy indicated that mainly wormlike cylindrical micelles were formed, even with highly hydrophilic polymers. The alkylated polymer exhibited no cytotoxicity, and their antioxidant abilities were evaluated by the ß-carotene bleaching method. Only 0.049 mol equivalents of poly(Arb)-C830 to linoleic acid was sufficient to preserve the ß-carotene.

One-pot synthesis of linear-hyperbranched amphiphilic block copolymers based on polyglycerol derivatives and their micelles.

This paper describes the one-pot synthesis of a polyglycidol (PG)-based polymer, poly(ethoxyethyl glycidyl ether) (PEEGE)-b-[hyperbranched polyglycerol (hbPG)-co-PEEGE]x/y, its micelle formulation, and the ability to encapsulate a model therapeutic molecule. Amphiphilic block copolymers were prepared by the sequential addition of ethoxyethyl glycidyl ether (EEGE) to glycidol. The composition of the block copolymers varied from 62:38 to 92:8. Block copolymers with composition x:y≥66:34 were soluble only in organic solvents. Micelles were formulated by injection of deionized water into a tetrahydrofuran block copolymer solution with or without pyrene as a model hydrophobic molecule. The critical micelle concentration was 18.2-30.9 mg/L, and the micelle size was 100-250 nm. The pyrene-containing micelle rapidly collapsed on acidic exposure, allowing conversion of hydrophobic PEEGE to hydrophilic PG, thus, facilitating the release of the encapsulated pyrene. Cytotoxicity data showed high biocompatibility of PG-based block copolymers, suggesting their potential as a drug delivery carrier.

Hyperbranched double hydrophilic block copolymer micelles of poly(ethylene oxide) and polyglycerol for pH-responsive drug delivery.

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.