A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation

Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf®) is an FDA-approved keystone immunosuppressant for preventing rejection. However, it undergoes extensive first-pass metabolism has a narrow therapeutic window, which leads to erratic bioavailability toxicity. Local delivery TAC directly into graft, instead systemic delivery, can improve safety, efficacy, tolerability. Macrophages have emerged as promising targets their increased levels correlate with poor prognosis post-transplantation. Here, we present locally injectable drug platform macrophages, where incorporated colloidally stable nanoemulsion then formulated reversibly thermoresponsive, pluronic-based nanoemulgel (NEG). This novel formulation designed undergo sol-to-gel transition at physiological temperature sustain release in situ site local application. We also show that TAC-NEG mitigates proinflammatory cytokines nitric oxide from lipopolysaccharide (LPS)-activated macrophages. To best our knowledge, this first TAC-loaded demonstrated anti-inflammatory effects on macrophages vitro.