Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Non-Human Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol
Technical Report,15 Sep 2018,14 Sep 2019
Massachusetts General Hospital Boston United States
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The focus for Year 3 was to study the controlled release of tacrolimus FK506 from a polymeric local delivery system PLDS both in vitro and in vivo and the stability of the devices in storage. In the in vivo studies, the PLDS released a large amount of tacrolimus, a first in the field which often suffers from low levels of release. Laminated PLDS devices were developed to reduce the initial burst of drug in vivo while improving the controlled release profile. A subcutaneous rat model was initiated to efficiently characterize the in vivo release profile of there formulated devices, which now show burst-free controlled release over 7 days in vivo. The release profile observed in vivo correlates to prior in vitro results which is beneficial for screening devices in the future. Long-term storage of the devices leads to a reduction in the release rate of the drug through loss of the molecular dispersion within the film. This helps control the early release rate and provide a more consistent release over time.
- Medicine and Medical Research