Drug Delivery System

[title in Japanese]

[in Japanese]

2002 Volume 17 Issue 2 Pages 83
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.83

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[title in Japanese]

[in Japanese]

2002 Volume 17 Issue 2 Pages 84
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.84

JOURNAL FREE ACCESS

Download PDF (198K)
Paradigm shift in dosage determination of anticancer agents—Dosage based on MTD to tumor size

Hiroshi Maeda

2002 Volume 17 Issue 2 Pages 88-93
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.88

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Traditional anticancer agents are mostly cytotoxic and small in molecular size. They distribute indiscriminately throughout the body, thus the high doge used in patients results in severe toxicity. Dose setting is based on maximum tolerable dose (MTD) ; and no way to escape the side effect at this dose. In contrast, polymeric drugs or microparticulates accumulate predominantly incancer tissue, if not 100%, which the mechanism is based on EPR-effect, Mechanism of EPR-effect is also described in the text. In any events, the dose should be based on the size of tumor ; large tumor needs large amount of drug. Such a good example is SMANCS/Lipiodol giver arterially for hepatoma ; this method can achieve a tumor/blood ratio of 2000, almost like missile. Accordingly, its good clinical result depends on dosing regimen based on tumor size. This concept will be appreciated as more such drugs with highly effective targeting become available.

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Personalized targeting cancer chemotherapy with SMANCS/lipiodol and the points of this therapy

Takao Inutsuka, Akinori Nagamitsu, Michio Kawasuji

2002 Volume 17 Issue 2 Pages 94-102
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.94

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Targeting cancer chemotherapy with SMANCS/Lipiodol for hepatocellular carcinoma has been used for more than 20 years. We believe it is important to reconfirm the characteristics of SMANCS/Lipiodol, and refine the method of administration and management of adverse effects in order to achieve satisfactory outcome. In this report, we reveal some clinical cases not only HCC but also other malignant solid tumors through our experience of 20 years. We experienced great many patients who received the arterially targeted cancer chemotherapy with SMANCS/Lipiodol for 20 years, so we would like to introduce various cases of different kinds of cancers and organic features when we perform arterial administration of SMANCS/Lipiodol.

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Genetic polymorphism of drug metabolizing enzymes and their role in individual drug therapy

Yasushi Yamazoe, Kiyoshi Nagata

2002 Volume 17 Issue 2 Pages 103-112
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.103

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Genetic polymorphism of drug metabolizing enzymes such as cytochrome P450 influences individual drug efficacy and safy through the alteration of pharmacokinetics and disposition of drugs. Considerable amounts of data are now accumulated for allelic differences of various enzymes. Here, current understanding of genotype information is summarized for their use on individual optimization of drug therapy.

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Side effects and its prevention in anticancer treatment

Kiyohiko Hatake

2002 Volume 17 Issue 2 Pages 113-118
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.113

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Anticancer drugs have been developing, and side effects of those drugs should be prevented. Many kinds of side effects have been reported, but we do not predict them. Side effects, including cardiac toxicity, nephrotoxicity, and neurotoxicity are known. As DNA microarray techniques has been developed well it is now applicable to predict side effects using single nucleotide polymorphism (SNP). To prevent side effects, development of new drugs or novel drug delivery system will provide us possibilities for future. Monoclonal antibodies or tyrosine kinase inhibitors are novel modalities to predict efficacy and side effects. Drug resistance or infusion-related syndrome has to be analyzed, For instances, CD 13 is a molecule that degrades the N-terminal residues of endothelial interleukin-8 and will be resistant to apoptotic signal. In this case we add CD 13 inhibitor, such as ubenimex, and it will give us a new therapy to treat CD 13-positive leukemia cells. Such research will be important to circumvent resistance or side effects. Liposome technologies for doxorubicin or cisplatin will give us less side effects. Small molecules that interferes cell cycle will be researched quickly.

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A navel gene expression profiling system using quantitative PCR—For clinical research and drug development

Tatsuya Kawaguchi, John C. Cheronis, Hiroaki Mitsuya

2002 Volume 17 Issue 2 Pages 119-126
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.119

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Innovation of gene technologies such as DNA microarray and real-time PCR has made it possible to quantitatively measure the expression of multiple genes. Such new technologies are expected to advance clinical medicine and pave new avenues for drug development. Source Precision Medicine^TM, a biotechnology company with which we have been working, has recently established a novel gene-expression profiling system using quantitative PCR in order to construct data bases of genetic profiles of individual patients upon therapy and disease progression. We here describe the system and recent data of the gene profiles associated with inflammatory processes, and discuss advantages of the use of the system for diagnosis/therapy and drug development.

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A new drug delivery system using plasma-irradiated pharmaceutical aids

—X controlled-release of theophylline from plasma-irradiated double-compressed tablet composed of poly(styrene-maleic anhydride) or poly(styrene-maleic acid) as a single wall material

Shin-ichi Kondo, Kousuke Ito, Yasushi Sasai, Masayuki Kuzuya

2002 Volume 17 Issue 2 Pages 127-133
Published: March 10, 2002
Released on J-STAGE: December 26, 2008

DOIhttps://doi.org/10.2745/dds.17.127

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As a part of the development of the DDS device using plasma-irradiated polymer, the utility of poly(styrene-maleic anhydride) (SMAn) and poly(styrene-maleic acid) (SMA) was investigated. From the results of plasma degradation tests and the electron spin resonance (ESR) studies on plasma-irradiated SMAn and SMA, it was found that they were of intramolecular bifunctionality, cross-linkable phenyl group and degradable maleic anhydride or maleic acid group as an effect of plasma irradiation. Using these plasma characteristics, controlled-release tablets were designed by argon plasma irradiation on the outer layer of double-compressed tablet prepared from theophylline as a core material and SMAn or SMA as a single wall material. The dissolution profiles of theophylline from plasma-irradiated double-compressed tablet were sufficiently modified in comparison with one of non-plasma-irradiated tablet, depending on the set of chosen plasma operational conditions.

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