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

目的：目的：研制乳酸/乙交酯共聚物纳米球（PLGA纳米球）系统，以提高他克莫司口服给药后的吸收，增强其生理和免疫抑制活性。LEW/SsN大鼠以4.8 mg/kg（n=5）他克莫司含量的剂量给予PLGA纳米球，通过单次口服给药实现长期持续释放。LEW/SsN大鼠通过单次口服给予PLGA纳米球，剂量为4.8 mg/kg（n=5）他克莫司含量，以阐明PLGA纳米球在器官中摄取的主要部位。在大鼠心脏移植模型中，受者在术后第一天以4.8mg/kg（n=5）他克莫司含量的PLGA纳米球隔日一次口服给药，持续2周，与常规形成每天一次持续2周相比。结果：PLGA纳米微球的AUC和t1/2β（半衰期）值均显著高于常规制剂（P<0.01）。PLGA纳米球和常规制剂之间的器官他克莫司水平无显著差异。然而，有没有显着差异之间的移植物存活率PLGA纳米球，每隔一天和传统的配方，everyday.Conclusion：PLGA纳米球显示了一个连续的平面浓度分布2天后，在目前的研究中，一个单一的口服给药。这一发现可能表明，可以每2天给予一次PLGA纳米球。

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.