DL-Lactide/Glycolide Copolymer Nanosphere To Improve Oral Delivery Of Tacrolimus

DL-丙交酯/乙交酯共聚物纳米球改善他克莫司的口服给药

• 批准号: 15591355
• 负责人: UNO Takeji
• 金额: $ 1.86万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-15591355/
• 关键词: DL-lactide; glycolide copolymer nanospheres; tacrolimus; sustained release drug delivery system; ポリ乳酸-グリコール酸共重合体; ラット心移植; 経口剤; 局所免疫抑制; ポリ乳酸グリコール酸共重合体; 薬物担体; ラット小腸移植

Objective : To develop DL-lactide/glycolide copolymer nanospheres (PLGA nanoshere) system to improve tacrolimus absorption and prolomg the physiological and immunosuppressive activity following oral administration.Methods : We prepared PLGA nanosphere. LEW/SsN rats were given PLGA nanosphere at a dose of 4.8 mg/kg (n=5) tacrolimus contents, by a single oral administration to achieve sustained release over a long period. LEW/SsN rats were given PLGA nanosphere by a single oral administration at a dose of 4.8 mg/kg (n=5) tacrolimus contents to clarify the main site of PLGA nanosphere uptake in the organs. In the rat heart transplantation model, the recipients were given PLGA nanosphere at a dose of 4.8 mg/kg (n=5) tacrolimus contents by a single oral administration every other day for 2 weeks on the first day after operation compared with conventional formation every day for 2 weeks. Overall survival days of grafts were compared.Results : The value of AUC and t_<1/2β>(half life of elimination phase) in the PLGA nanosphere was significantly higher (p<0.01) than in the conventional formulation. There were no significant differences in tacrolimus levels of organs between PLGA nanosphere and conventional formulation. However, there were no significant differences in graft survival between PLGA nanosphere, every other day and conventional formulation, every day.Conclusion : PLGA nanosphere revealed a continuous flat concentration profile for 2 days after a single oral administration in the current study. This finding may suggest that it is possible to administer PLGA nanosphere one time per 2 days.

目的：开发DL-丙二醇/糖苷共聚物纳米球（PLGA纳米球）系统，以改善他克莫司的抽象并促进口服后的物理和免疫抑制活性。方法：我们准备了PLGA纳米圈。单个口服给药以4.8 mg/kg（n = 5）的剂量为4.8 mg/kg（n = 5）的剂量给予LEW/SSN大鼠，单个口服给药，以长期实现持续的释放。通过单个口服给药以4.8 mg/kg（n = 5）他克莫司含量的剂量给予LEW/SSN大鼠，以阐明器官中PLGA纳米圈的主要摄取部位。在大鼠心脏移植模型中，将接受者以4.8 mg/kg（n = 5）他克莫司含量的剂量为PLGA纳米圈，每隔一天一次口服一次，在手术后的第一天，与每天的常规形成相比，在两周后的第一天，两周一次。比较了移植物的总生存日：PLGA纳米球中AUC和T_ <1/2β>（消除阶段的一半寿命）的值明显高于常规公式（p <0.01）。 PLGA纳米球和常规配方之间的他克莫司的器官水平没有显着差异。然而，每天的二天和常规配方在PLGA纳米球之间没有显着差异。结论：PLGA纳米球显示在当前研究中单个口服后2天连续扁平浓度谱。这一发现可能表明可以每2天一次给予PLGA纳米球一次。

项目成果

Miyamoto, Y, Uno T, Yamamoto H, et al.: "Pharmacokinetic and Immunosuppressive Effects of Tacrolimus- Loaded Biodegradable Microspheres"Liver Transplantation. 10・3. 392-396 (2004)

Miyamoto, Y, Uno T, Yamamoto H, et al.：“负载他克莫司的可生物降解微球的药代动力学和免疫抑制作用”10・3 (2004)。