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We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed a dual temperature- and pH-responsive polymeric micelle composed of a temperature-responsive corona segment with poly(N-isopropylacrylamide-co-dimethylacrylamide) [P(NIPAAm-co-DMAAm)] and a pH-responsive core segment with poly[2-(diisopropylamino)ethyl methacrylate] (PDPA). A dual temperature- and pH-responsive amphiphilic diblock copolymer was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. The dithiobenzoate end-group was removed with radical-induced ester exchange. This copolymer formed nano-sized micelles in aqueous solution, and encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelles exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above the phase transition temperature. A transition from neutral to positive charge, leading to micelle disassembly, accelerated the release of Nile red as a model drug. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature- and pH-responsive micelles against human cervical cancer HeLa cells was significantly greater at 42 °C than at 37 °C, while no significant temperature-dependent cytotoxicity was observed with DOX-loaded micelles that were only temperature-responsive. This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.

Polyrotaxane fibers prepared with wet spinning of polyrotaxane consisting of poly(ethylene glycol) and cyclodextrins were cross-linked with two different cross-linking reagents, i.e., divinyl sulfone (DVS) and ethylene glycol diglycidyl ether (EGDE), to improve the tensile properties of the fibers. By cross-linking with DVS, the values for the tenacity at break and the initial modulus were increased with cross-linking time, while the elongation at break was improved only moderately. On the other hand, drastic improvements in elongation at break were observed after EGDE cross-linking, up to 645% of its original length, although the tenacity at break and the initial modulus showed only slight improvements. After cross-linking, only minor changes in the degree of crystallinity of the fibers were observed by wide-angle X-ray scattering measurements., Article, TEXTILE RESEARCH JOURNAL. 80(12):1131-1137 (2010)

The preparation of polyrotaxane fibers by wet spinning of polyrotaxane, consisting of poly(ethylene glycol) (PEG) and α-cyclodextrins (α-CDs), was examined using three different types of dope solvents: dimethylacetamide (DMAc) containing 8 wt% lithium chloride (LiCl), dimethylformamide (DMF) containing 8 wt% LiCl, and dimethylsulfoxide (DMSO). In DMSO, polyrotaxane concentrations of 20 and 30 wt% were favorable for the smooth spinning of fibers with sufficient tenacity, while other polyrotaxane concentrations (10, 15, and 40 wt%) were unsuitable for the wet spinning of durable fibers. All of the fibers had nearly identical scanning electron microscopy (SEM) images and X-ray diffraction patterns. Although the values for tenacity at break and initial modulus also were similar for all fibers, elongation at break of fibers from DMSO was higher than the values for the other two fibers. The poorer physical properties of the latter two fibers may be affected by the slight amount of lithium salt remaining in the fibers.

Polyrotaxane fiber and polyrotaxane/cellulose blend fibers were prepared by wet-spinning of the polyrotaxane or polyrotaxane/cellulose blend solution dissolved in the new solvent system, i.e. dimethylacetamide/lithium chloride (DMAc/LiCl), into methanol and a subsequent annealing. In the resultant polyrotaxane/cellulose fiber, some undissolved rodlike cellulose microcrystals were oriented along with the fiber axis, resulting in formation of nanocomposite-like structure. From tensile measurements, it was found that the Young's modulus and tensile strength of the fibers with polyrotaxane/cellulose ratio of 1:1 and 2:1 were higher than those of the pure cellulose fiber. Although the mechanical properties of the fiber with polyrotaxane/cellulose ratio of 4:1 and the pure polyrotaxane fiber were lower than those of the pure cellulose fiber, these fibers showed significantly large strain at break (up to 90% strain), presumably due to the sliding of the cyclodextrin rings of the polyrotaxane in the fibers.

Polyrotaxane (PR), a typical example of topological supramolecular architecture, consists of multiple cyclic molecules threaded onto a linear polymer backbone and capped with bulky end-groups. The PR system of polyethylene glycol and α-cyclodextrin (α-CD) has been extensively studied for its facile synthesis, unique molecular structure, and possible applications for various smart materials. We have previously demonstrated the fabrication of PR-based fibers without chemical cross-links by wet spinning of PR solution. In this paper, we investigate the crystal structure of α-CDs in PR fibers and the effect of drawing on it. The α-CDs in PR fiber are found to form hexagonal channel-type structure. The drawing process promotes formation of the packing arrangement of α-CDs in the c-axis because of the sliding of α-CD molecules along the polymer backbone. In addition, we demonstrate the preparation of an elastomeric PR film having similar network structure to the fibers and ethylene glycol oligomer as plasticizer.