Intelligent approach to construct intravenously injectable nanoparticles by interface transference properties

通过界面转移特性构建静脉注射纳米颗粒的智能方法

• 批准号: 15300171
• 负责人: TAKEOKA Shinji
• 金额: $ 5.82万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15300171/
• 关键词: Drug Delivery System; Bioconjugate chemistry; Biomaterials; Biofuncional materials; Bio-related polymer chemistry; Molecular assembly; Linosomes; Lipopolysaccharide; バイオコンジュケイト; 生体適合材料; 機能性高分子化学; インテリジェント材料; 核酸・蛋白質・糖化学

In present study, the knowledge accumulated by development of an artificial red blood cell or artificial platelets is exploited. We incorporated the recognition sites, which were made of ligands such as receptor proteins and peptides or sugar chains, into the surface of these nano-particles by a simple method, aiming to making it intelligent and effective in a medical treatment. In 2003, we synthesized the large amount of the amino acid-type lipids with two chains, and examined the conjugation method of these lipids to oligopeptides or oligosaccharides by a solid-phase synthesis method. Then, we obtained the polyethyleneglycol-lipids with two or four alkyl chains. Furthermore, the functional PEG-lipid was synthesized in a large scale from a-maleimide, ω-succinimide PEG. Moreover, we also synthesized the functional PEG-lipids by coupling the alkyl chains in the disulfides bond as being considered as the membrane expanding packing, and combined maleimide PEG at the terminal. Next, for th … More e liposomes contaminated with lipopolysaccharide(LPS) as a bioactive substance, a surfactant treatment was applied to quantitatively measure the LPS content by using the interfacial transfer phenomenon. In 2004, the maleimide PEG lipid was introduced on the liposome surface by the interfacial transfer method. Then, proteins of which molecular weight was different (Lactalbumin(Mw : 14kDa), rHSA (66.5kDa), IgG (150kDa), Ferritin (460kDa), and Thyrogrobulin (670kDa)) were combined to the PEG lipid and the rate of the resulting protein-lipids isolated from the liposome surface (interfacial transfer) was analyzed. As a result, good correlation was acquired between the number and length of the alkyl chains of the PEG lipid, and the protein molecular weight. Moreover, if a recognition molecule (saccharide or oligopeptide) is conjugated on the liposome surface and then modified with PEG chains, the recognition ability is considered to be masked with the PEG chain. However, it was clarified that functional expression was switched when PEG lipids was isolated from the surface (interfacial transfer). From the above results, the novel drug carriers which can control pharmacokinetic can be designed by utilizing the isolation phenomenon of the PEG-lipids or protein-conjugated PEG-lipids modifying the liposome surface. Less

在目前的研究中，探索了人造红细胞或人造血小板所积累的知识。我们通过一种简单的方法将识别位点纳入了这些纳米粒子的表面，这些识别位点是由受体蛋白和胡椒粉或糖链制成的，旨在使其在医疗治疗中聪明有效。在2003年，我们用两个链合成了大量的氨基酸型脂质，并通过固相合成方法检查了这些脂质与寡肽或寡糖的共轭方法。然后，我们获得了带有两个或四个酒精链的聚乙烯甘油脂。此外，功能性PEG脂质是由A甲酰亚胺ω-核苷peg大规模合成的。此外，我们还通过将二硫键键中的酒精链耦合被认为是膜膨胀的填料，并在末端构成了马来酰亚胺PEG，从而综合了功能性PEG脂质。接下来，对于以脂多糖（LPS）为生物活性物质污染的更多脂质体，使用界面转移现象对表面处理进行定量测量LPS含量。 2004年，通过界面转移方法在脂质体表面引入了马来酰亚胺PEG脂质。然后，其分子量的蛋白质不同（乳蛋白蛋白（MW：14KDA），RHSA（66.5KDA），IgG（150KDA），铁蛋白（460KDA）和甲状腺素（670KDA）（670KDA）与PEG Lipid ripId rips rip rip rip rip-lip组合在一起。分析（界面转移）。结果，在PEG脂质的烷基链的数量和长度与蛋白质分子量之间获得了良好的相关性。此外，如果将识别分子（糖或寡肽）偶联在脂质体表面，然后用PEG链进行修饰，则认为识别能力被认为是用PEG链掩盖的。然而，澄清说，从表面分离出PEG脂质时（界面转移）切换了功能表达。从上述结果中，可以通过使用PEG脂质的隔离现象或蛋白质偶联的PEG脂质来修饰脂质体表面的新型药物载体。较少的

项目成果

Recognition Properties of Polymerized Albumin Particles and Phospholipid Vesicles Bearing Recognition Proteins

聚合白蛋白颗粒和携带识别蛋白的磷脂囊泡的识别特性

• 发表时间: 2004
• 作者: H.Nonaka;M.Kurihara;S.Takeoka
• 通讯作者: S.Takeoka

親-疎水性バランスの異なるポリエチレングリコール脂質によるリポソーム表面修飾度の制御

使用具有不同母体疏水平衡的聚乙二醇脂质控制脂质体表面修饰的程度

• 发表时间: 2005
• 作者: 久保田恒平;金澤秀雄;久本秀治;武岡真司
• 通讯作者: 武岡真司

Construction of artificial red blood cells and artificial platelets as functional molecular devices

构建人工红细胞和人工血小板作为功能性分子装置

• 发表时间: 2005
• 作者: 長野;前田;八木谷;田澤他;Shinji Takeoka
• 通讯作者: Shinji Takeoka

Sakai H, Hisamoto S, Fukutomi I, Sou K, Takeoka S, Tsuchida E: "Detection of lipopolysaccharide in hemoglobin-vesicles by Limulus amebocytelysate test with kinetic-turbidimetric gel clotting analysis"J Pharm Sci.. 93(2). 310-321 (2004)

Sakai H、Hisamoto S、Fukutomi I、Sou K、Takeoka S、Tsuchida E：“通过鲎阿米巴细胞溶解物测试和动力学比浊凝胶凝固分析检测血红蛋白囊泡中的脂多糖”J Pharm Sci.. 93（2）。

機能性分子素子としての人工赤血球・人工血小板の構築

构建人造红细胞和血小板作为功能性分子装置

• 发表时间: 2005
• 作者: 武岡真司