Various stimuli (thermal, light, magnetic, etc.)-responsive materials are widely used as DDS carriers. These materials are very useful for realizing innovative DDS; however, their utilization may require investment on infrastructure. In this article, a novel gel carrier that release drugs in response to mechanical force generated by patients' hands is introduced. The gel consisted of sodium/calcium alginate and cyclodextrin-crosslinker, and ondansetron was loaded as a model drug. The drug release occurred in response to compression that mimicked the force applied by patients' hands. In addition to contribution to QOL, this DDS can be a novel dosing methodology for patients in developing countries and those lacking in lifelines due to disaster.

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The conventional anticancer agents often have some unexpected limitations such as poor distribution, tissue damage, and lack of target specificity. In order to overcome these problems, the drug delivery technique to tumor cells has attracted considerable attention. Meanwhile, the widespread use of folic acid (FA) as a tumor-targeting ligand has been known, because folate receptor-α (FR-α) overexpresses in various kinds of epithelial tumor cells. On the other hand, methyl-β-cyclodextrin (M-β-CyD) is acknowledged to disrupt the structures of lipid rafts, through the extraction of cholesterol from the microdomains. Grosse et al. reported that intraperitoneal administration of M-β-CyD had antitumor activity in human tumor xenografted athymic nude mice. However, the antitumor activity of M-β-CyD has a lack of a tumor cell-selectivity. Therefore, in the present study, to make an attempt to confer a tumor cell-selectivity to M-β-CyD, we newly synthesized folate-appended M-β-CyD (FA-M-β-CyD), and evaluated the potentials as its novel antitumor agent. FA-M-β-CyD showed the potent antitumor activity in various FR-α-positive cells such as KB cells, Ihara cells and M213 cells, but not in FR-α-negative cells, A549 cells. In sharp contrast to M-β-CyD, FA-M-β-CyD did not change the DNA content, but significantly elevated the mitochondrial transmembrane potential in KB cells. Additionally, activation of caspase-3/7 in KB cells did not occur after treatment with FA-M-β-CyD, indicating that FA-M-β-CyD caused cell-death in a apoptosis-independent pathway. FA-M-β-CyD induced the formation of autophagic vacuoles in KB cells. In addition, the antitumor activity of FA-M-β-CyD, not M-β-CyD, was inhibited by the addition of chloroquine and bafilomycin A1, autophagy inhibitors, in KB cells. A single intravenous injection of FA-M-β-CyD drastically inhibited the tumor growth and significantly improved survival rate, in Colon-26 cells-allografted or M213 cells-xenografted mice. In conclusion, the present study demonstrated the potentials of FA-M-β-CyD as a novel tumor-selective anticancer agent, due to the FR-α-mediated cellular uptake. The present results will give useful information for design and development for novel antitumor drug carriers and antitumor drugs based on CyDs.

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Cationic oligopeptides, which are mainly composed of basic amino acids such as arginine, are internalized into cells via macropinocytosis. We designed a novel polymer: cationic oligopeptide-linked polymer, with the expectation that the polymers will remain on the cell membrane and poorly membrane-permeable molecules are continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone without the concomitant cellular uptake of the polymers. Here, we report the potential of oligoarginine-linked polymers, mainly poly(N-vinylacetamide-co-acrylic acid) modified with D-octaarginine, as a new class of penetration enhancers.

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Diabetes is not an infectious disease but its increasingly rapid and worldwide prevalence has been recognized as "pandemic". Despite the necessity for continuous and accurate glycemic control in the management of insulin dependent diabetes mellitus, the current palliative treatment relies almost solely on the patient-self injection of insulin, which not only impinges on quality of life of the patients but also fails to precisely control dose of insulin where the overdose must be strictly avoided otherwise causing serious hypoglycemia. Development of self-regulated insulin delivery systems is a long-standing challenge of materials science, for which exploitations of glucose oxidase and sugar-binding lectin are two prevalent strategies to install the function of glucose-sensitivity. These protein-based components, however, intolerant of long-term use and storage with their denaturing and cytotoxic natures, are hardly suitable for any implantable applications thus have not yet been in clinical usage to date. This review intends to provide an overview of the current efforts to develop a thoroughly synthetic alternative making use of a phenylboronic acid derivatized polyacrylamide gel.

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In this review, I introduce the function and the application field of the self-oscillating polymer system that can drive without the external stimuli under the constant temperature conditions. The driving force of the self-oscillating polymer system is produced by the dissipating chemical energy of the Belouzov-Zhabotinsky (BZ) reaction. The BZ reaction is well known as an oscillating reaction accompanying spontaneous redox oscillations to generate a wide variety of nonlinear phenomena, e.g., a target or spiral pattern in an unstirred solution, and periodicity, multi-periodicity, or chaos in a stirred solution. The overall process of the BZ reaction is the oxidation of an organic substrate by an oxidizing agent in the presence of the catalyst under strong acidic condition. In the BZ reaction, the metal catalyst undergoes spontaneous redox self-oscillation, and it changes the solubility from hydrophilic to hydrophobic at the same time. The polymer system realized the self-oscillation by synchronize with the periodical solubility change of the Ru catalyst moiety. In recent years, the self-oscillating polymer system improved the molecular design in order to apply to micro fluid devices. The micro fluid devices with the self-oscillating polymer actuator do not need a power supply and external control devices.

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The design of biomaterials that can modulate the immune system (immunobioengineering) is an emerging field. Examples are the engineering of material surfaces to induce or prevent complement activation, the engineering of antigen or adjuvant carriers for subunit vaccine delivery, and the engineering of microenvironments to determine the interaction kinetics of mature dendritic cells and naïve T cells. One of the major advantages of material-based therapy is the cost-effectiveness or availability in the low-infrastructured area; e.g., wet formulations and unrefrigerated storage, preferably needle-free administration routes and few doses, and materials that can be easily manufactured and contain a minimal number of biological molecules. In this review, we describe the current state of immunobioengineering from the materials science viewpoints, and give a perspective on its current and future directions.

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