Tomoko Takizawa

Niigata University Medical and Dental Hospital

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Drug and Gene Delivery by “Bubble Liposomes” and Ultrasound

YAKUGAKU ZASSHI (2007)

Kazuo Maruyama Ryo Suzuki Tomoko Takizawa Naoki Utoguchi Yoichi Negishi

Gene therapy has a potentiality for treatment of cancer and diseases from genomic defects. It is important to select a vector which has good potency in terms of gene transduction efficiency, and is safe and easy to apply. Many researchers have attempted to develop an effective gene delivery carrier. Recently, it was reported that microbubbles, which are ultrasound (US) contrast agents, improved the transfection efficiency by cavitation with US exposure. However, microbubbles had problems with stability and targeting ability. To solve these problems, we focused on liposomes that had many advantages such as being stable and safe in vivo and easily modifying targeting ligand. We succeeded in preparing the liposomes ("Bubble liposomes" (BLs)) entrapping perfluoropropane gas which was utilized for contrast enhancement in ultrasonography. In this study, we assessed the feasibility of BLs as gene delivery carrier utilized cavitation by US exposure. BLs could deliver plasmid DNA to various cell types in vitro by combining with US without cytotoxicity. To evaluate the ability of BLs to in vivo gene delivery, we attempted to deliver plasmid DNA into the femoral artery. The gene expression at this artery treated with BLs and US combination was higher than with US only, BLs without US or Lipofectamine 2000. This result suggested that Bubble liposomes could quickly deliver plasmid DNA into the artery even under conditions of short contact time between BLs and the endothelial cells and the existence of the bloodstream and serum. These results suggested that BLs might be a non-invasive and effective carrier for gene delivery.

Lipofectamine

10.1248/yakushi.127.781

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Citations (11)

Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound

Journal of Controlled Release (2008)

Yoichi Negishi Yoko Endo Tetsuya Fukuyama Ryo Suzuki Tomoko Takizawa

10.1016/j.jconrel.2008.08.019

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Citations (122)

Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles targeting activated platelet glycoprotein IIb/IIIa complex—in vitro and in vivo study

International Journal of Cardiology (2010)

Kohsuke Hagisawa Toshihiko Nishioka Ryo Suzuki Tomoko Takizawa Kazuo Maruyama

10.1016/j.ijcard.2010.07.016

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Citations (28)

Targetability of PEG-immunoliposomes in vivo and the preparation of adriamycin encapsulated PEG-immunoliposomes.

Drug Delivery System (1996)

Tomoko Takizawa Kazuo Maruyama Motoharu Iwatsuru

Drug delivery to specific cells by immunoliposomes represents a potentially attractive mode of therapy. However, though immunoliposomes are effective in specific binding to target cells in vitro, their targeting efficiency in vivo is relatively low. We have recently developed a new type of long-circulating immunoliposomes (Type C) which can effectively bind to the designated target site in vivo. This was achieved by the use of newly synthesized DSPE-PEG-COOH to couple antibodies directly to the distal terminal of PEG chains, which allow the liposome to evade the RES uptake and achieve prolonged circulation. Liposomes were prepared from ePC and CH (2 : 1, m/m)containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amount of antibody molecules per liposome. PEG-COOH-liposomes without antibodies showed prolonged circulation time and reduced RES uptake owing to the presence of PEG. The degree of lung binding of 34A-Type C was increased with increasing coupling amount of antibody. Antibody density is an important factor for target binding. We established the preparation of adriamycin (ADR) encapsulated 34A-Type C immunoliposomes. ADR encapsulation was done by employing an ammonium sulfate (AS) gradient method. PEG-COOH liposomes were prepared in 120 mM AS and attached 34A to make 34A-Type C. External medium of liposome was replaced to 120 μM AS for the creation of AS gradient between inside and outside of liposome membrane and ADR solution was added into external medium. The ADR loading efficiency was 95%. ADR level in lung after i.v. injection of ADR-34A-Type C was much higher than that of control ADR liposome and free ADR.

10.2745/dds.11.405

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Citations (0)

Development of PEG-Liposomal Formulation Encapsulating Anti-cancer Drugs

MEMBRANE (2005)

Kazuo Maruyama Atsushi Yamashita Ryo Suzuki Tomoko Takizawa Naoki Utoguchi

10.5360/membrane.30.298

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Citations (1)

Possibility of active targeting to tumor tissues with liposomes

Advanced Drug Delivery Reviews (1999)

Kazuo Maruyama Osamu Ishida Tomoko Takizawa Kunikazu Moribe

10.1016/s0169-409x(99)00042-3

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Citations (211)

Development of Site Specific Gene Delivery System with Sonoporation

YAKUGAKU ZASSHI (2008)

Ryo Suzuki Yusuke Oda Eisuke Namai Tomoko Takizawa Yoichi Negishi

In gene therapy, it is important to develop an effective and safe gene delivery system. Especially, from the viewpoint of reducing side effects, gene delivery into a specific site is essential. We previously, developed liposomal bubbles (Bubble liposomes) containing perfluoropropane. Bubble liposomes were useful as ultrasound enhanced gene delivery tools in vitro and in vivo. In this review, we introduced the characteristics of Bubble liposomes as ultrasound imaging agents and ultrasound enhanced gene delivery tools. Bubble liposomes worked as ultrasound imaging agents in cardiosonography. In addition, their combination with ultrasound exposure was able to deliver plasmid DNA in the femoral artery. The gene expression was only observed at the site of ultrasound exposure. Moreover, the gene delivery by Bubble liposomes and ultrasound exposure was more efficient than that by conventional lipofection method using Lipofectamine 2000. Therefore, it was suggested that Bubble liposomes might be a new class of tools for site specific gene delivery.

Sonoporation

Lipofectamine

10.1248/yakushi.128.187

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Citations (7)

Long-circulating liposomes.

Drug Delivery System (1994)

Tsutomu Yuda Kazuo Maruyama Tomoko Takizawa Motoharu Iwatsuru

Liposomes have attracted a considerable amount of interest for potential use as a drug delivery system due to their suitable characteristics. However, the predominant uptake of liposomes by the reticuloendotherial system (RES) and a resulting rapid clearance from circulation have been a major obstacle in any attempt to deliver liposomes to cells, tissue or organs other than the RES. One of the current efforts is to overcome the above kinetic barrier by manipulating the liposome characteristics. Some attempts have been made to reduce the RES uptake by surface modification with glycolipids or synthetic polymers. Especialy, incorporation of polyctyleneglycol-lipid derivatives(PEG) in liposome led to increased blood levels of liposomes and reduced uptake by the RES. In this review, various designs of PEG containing liposomes are presented, characterization of PEG-liposomes and possible mechanisms of action are discussed. It is suggested here that the primary mechanism by which PEG molecules alter the biodistribution of liposomes in vivo involeves an inhibition of the association of blood components(opsonin ?) to liposomes, resulting in a reduced rate of clearance of liposomes from the circulation. The many advantages of long-circulating liposomes, such as PEG-liposome, make them excellent candidates as drug delivery systems for sustained drug release or drug targeting application.

Biodistribution

10.2745/dds.9.145

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Citations (24)

Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound

Journal of Controlled Release (2006)

Ryo Suzuki Tomoko Takizawa Yoichi Negishi Kohsuke Hagisawa Kumiko Tanaka

10.1016/j.jconrel.2006.09.008

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Citations (215)

Immunoliposomes as drug delivery carrier

Drug Delivery System (2004)

Ryo Suzuki Tomoko Takizawa Kazuo Maruyama

近年, 抗がん剤の薬物送達キャリアとしてPEG-リポソームが注目されている. このPEG-リポソームは血中滞留性にすぐれ, 腫瘍部位へのパッシブターゲティングが可能であるため, 抗がん剤の副作用軽減ならびに抗腫瘍効果増強が期待されている. 将来的に, このリポソーム製剤をさまざまな疾病治療に応用していくためには, 目的部位にアクティブターゲティング可能な性質をも付与する必要があると考えられる. この観点から, PEG-リポソーム表面を抗体で修飾したイムノリポソームが開発された. このイムノリポソームは, 細網内皮系回避能およびアクティブターゲティング能の両者を備えた理想的な薬物送達キャリアである. また, 最近では, 抗体修飾のみならず特定分子を認識する蛋白やペプチドを修飾したリポソームによるアクティプターゲティングも検討されている. そこで本稿では, がん治療を念頭に, アクティブターゲティング可能なリポソーム製剤について概説する.

10.2745/dds.19.539

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Citations (0)