This review explains correlation between drug delivery systems and micromachines with focusing on drug targeting. Micromachines are mm order-sized or smaller machinery for functions in microscopic scales. “Drug targeting machine” has been described in the micromachine field as one “dream machine” working in living bodies. On the other hand, this dream has been achieved to a considerable extent in the DDS field using nano-sized carrier systems such as liposomes, synthetic and natural polymers. These carriers can be recognized as molecular machines that made from macromolecules or made by association of molecules. This review summarizes recent advances in nano-sized drug carriers and the future perspective of drug carrier research and its developments in terms of nanotechnologies.

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Metastasis, the most characteristic nature of cancer, has been and still is a long-standing problem in cancer therapy. Irrespective of variety of extensive challenges consisting of clinical and basic researches, any clinically effective measure to control the metastasis has not yet been established. Recent advances in bioscience and biotechnology, however, strongly suggest that there are some promising approaches to antimetastaic treatments. Collaborative studies with clinicians, technologist and basic scientist will play a crucial role in obtaining fruitful results.

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Drugs are rapidly absorbed into the circulation when given intraperitoneally in a form of aqueous solution. Using the aqueous form of the drugs, it is difficult to maintain the drug concentration at a high level for a long period of time. To overcome the difficulty, drugs are given many times or in a great volume of aqueous solution at a time. Recent investigations have shown that intraperitoneally seeded cancer cells implant in some specific sites, such as milky spots, on the peritoneum in the early phase of peritoneal carcinomatosis. In order to target the cancer foci implanting in the specific sites, new types of DDS have been developed in which the drugs are formed into high molecules or small particles.

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The recent development of humanized monoclonal antibody has made antibody therapy, which has many theoretical attractions, an encouraging choice of treatment in hematology/oncology area. This article reviews the basic theory and clinical applications of major antibody therapy, including Herceptin, Rituxan and other antibodies of interest.

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Tumor metastasis involves multiple processes such as angiogenesis, invasion, cell adhesion, extravasation, cell growth etc. In order to develop the drug delivery systems aiming at overcoming tumor metastasis, it is necessary to evaluate the delivery systems employing appropriate experimental models which can mimic tumor metastasis in the body. The models are classified into two categories, i. e., in vitro and in vivo models in which, in general, cell culture systems and experimental animals are used, respectively. In vitro models are useful for the analysis of individual metastasis process at cellular level. On the other hand, overall metastasis can be assessed in in vivo models at whole body level. In this review, both in vitro and in vivo experimental metastasis models are reviewed. Finally, some approaches for preventing tumor metastasis using these experimental models are also discussed.

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Development of anticancer drugs provides the significant achievement in the clinical treatment. However most of the clinical antitumor drugs have severe side effects such as leukocytepenta. To reduce side effects and enhance antitumor activity, the delivery of antitumor reagent should be controlled. One of the most effective methods to control the pharmacokinetics is the conjugation of antitumor drugs with polymeric carriers. We have developed novel conjugates of DIVEMA (copolymer of divinyl ether and maleic anhydride) with anticancer drugs (adriamycin and methotrexate) and cytokine (TNF-α). The conjugates proved to have more effective than anticancer drugs against murine cancer models including solid tumors with less toxicity. Such polymeric conjugates proved to be effective to improve the body distribution of bioactive proteins, which are quickly hydrolyzed by proteolytic enzymes in vivo. As a model of protein, we have examined the anti-inflammatory activity of the conjugated of SOD (superoxide dismutase) with DIVEMA. Liver resection and liver transplantation needs the effective protection of ischemia-reperfusion injury, which leads to organ failure. Some attempts have been made for protect ischemia-reperfusion injury by means of SOD. Due to the short half-life in vivo of SOD alone (less than 5 min), the clinical effectiveness of SOD was quite limited. Through dynamic observation of the liver microcirculation using intra-vital microscopy techniques, we have evaluated the effect of DIVEMA-SOD on ischemia-reperfusion liver injury. DIVEMA-SOD showed protective effect of ischemia-reperfusion injury significantly as compared to SOD alone. The copolymer of DIVEMA provides the possibility for great achievement of with cytokines, and organ protection in the transplantation medicine.

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