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Open Access Treatment strategy for malignant bone soft tissue tumor by ph-reactive liposome based on new concept

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Asanuma is part of a project that seeks to develop a novel drug delivery system (DDS) by using a pH-sensitive liposome to target drugs. He believes that drug targeting is a particularly powerful strategy in tackling sarcomas. 'We have reported acidity within sarcoma tissues and have hypothesised that the acidity can be a tumour-specific phenomenon and thus, a therapeutic target in vivo. We hope to develop a new DDS by targeting the acidic areas in sarcoma tissue using a pH-sensitive liposome,' he says. The project's central goal is to develop a new DDS targeting sarcoma tissue to treat these rare cancers. Asanuma elaborates: 'Instead of seeking new targets or new drugs, we are trying to build a new DDS by drug targeting using a pH-sensitive liposome. Our research will prove that acidity can be therapeutic target using DDS for sarcoma treatment and higher levels of anti-cancer drugs can be delivered to sarcoma tissue with lower systemic side effects. This makes it feasible to use pH-sensitive liposomes for high risk patients due to the lower risks involved.' Existing approaches encounter difficulties as, 'Bone and soft tissue sarcomas are uncommon cancers and rarely have tumour-specific targets, making it difficult to develop targeted sarcoma therapies,' explains Asanuma. Using tissue pH levels as a target, Asanuma and his team were able to create a novel pH-sensitive liposome that can be used to encapsulate anti-cancer drugs and administered intravascularly. Due to the design of the liposomes, the drugs are then only released in acidic areas, such as the sarcoma tissues, allowing highly localised delivery of drugs to the desired regions. This means that much lower doses can be used, making them suitable for high-risk patients such as the elderly patients and patients of weak organ function. Asanuma's group have collaborated with Professor Tetsuro Yoshimura, Emeritus Professor at the Graduate School of Engineering, Mie University, on this project, in order to develop the liposomes that form such a critical part of their targeting strategy. Yoshimura, a liposome expert, invented the semi-automatic manufacturing equipment used to develop the pH-sensitive liposomes used in Asanuma's DDS. Egg yolk phosphatidylcholine and pH-sensitive phospholipid (which has a PEG-like group) were used to prepare the group's liposomes using vortex mixing methods made possible by Yoshimura's equipment. The resultant product was filtered through a 0.1 aem membrane to acquire passive targeting to sarcoma tissue through the enhanced permeability and retention (EPR) effect.
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Keywords: ACIDITY WITHIN SARCOMA TISSUES; BONE AND SOFT TISSUE SARCOMAS; DDS; DDS TARGETING SARCOMA TISSUE; DRUG TARGETING; EGG YOLK PHOSPHATIDYLCHOLINE; ENHANCED PERMEABILITY AND RETENTION (EPR) EFFECT; NOVEL DRUG DELIVERY SYSTEM; PH-SENSITIVE LIPOSOME; PH-SENSITIVE PHOSPHOLIPID; SARCOMAS; VORTEX MIXING METHODS

Document Type: Research Article

Affiliations: Mie University, Japan

Publication date: April 1, 2019

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