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

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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.