Albumin Based Nanomedicine for Enhancing Tacrolimus Safety and Lymphatic Targeting Efficiency

The increasing demand of organ transplantation and the frequent occurrence of transplant rejection necessitate the development of new therapies. Immunosuppressant marks an effective therapeutic strategy but is usually impeded by its toxicity, untargeted delivery to draining lymph node. The emergence of nanoformulations provides a possibly way to address these challenges. In this work, we prepared a novel human serum albumin (HSA) nanoformulation loaded with a well-known immunosuppressant tacrolimus (TAC) (termed TAC-HSA-NPs), via a simple self-assembly procedure of albumin in aqueous solution to enhance the solubility of TAC. By adjusting the molar ratio of HSA to TAC, we were able to take control of several key parameters of the obtained nanoparticles, such as loading capacity and particle size. Under the molar ratio of HSA:TAC = 1:10, TAC-HSA-NPs showed a mean size of 164 ± 51 nm with reliable pharmacokinetic stability, prolonged blood circulation time as well as decreased renal toxicity. More importantly, in vivo mice allo-heart transplantation verified the efficient lymphatic targeting of TAC-HSA-NPs, which is of crucial significance for immunosuppression in heart transplant recipients. Overall, our study proposed a new nanoformulation of TAC-HSA-NPs and confirmed the potential application in organ transplantation.