Degradation, Intra-Articular Biocompatibility, Drug Release, and Bioactivity of Tacrolimus-Loaded Poly(d-l-lactide-PEG)-b-poly(l-lactide) Multiblock Copolymer-Based Monospheres

The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)-b-poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic–hydrophilic block ratio. The monospheres were 30 μm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation. Rat knees were injected with three different doses of tacrolimus (10 wt %) loaded monospheres (2.5, 5.0, and 10 mg), contralateral control knees with saline. Micro-CT and histology showed no negative changes on cartilage, indicating good biocompatibility. Minor osteophyte formation was seen in a dose dependent fashion, suggesting local drug release and therapeutic action thereof. To investigate in vivo drug release, t...