Dissolvable microneedle-assisted transdermal administration of diacerein nanoparticles achieved satisfactory therapeutic effects in tendon-bone insertion repair by reducing oxidative stress and inflammation

Abstract

Tendon-bone insertion injuries are frequently encountered in sports medicine clinics, with the healing process posing a significant challenge within this field. When it comes to non-surgical interventions for such injuries, the use of local drug injections may carry the risk of damaging peripheral nerves and blood vessels. In this study, a simple dissolvable microneedle (DMN) patch loaded with diacerein (Dia) nanoparticles (DMN/PLGA@Dia) is established to achieve a constant delivery of Dia for enhancing tendon-bone healing. In vitro experiments demonstrate that Dia alleviates oxidative stress, reduces apoptosis, and prevents senescence in tendon cells, while also polarizing macrophages to the M2 phenotype. In a rat model of Achilles tendon-bone insertion injury, the application of DMN/PLGA@Dia enhances the regeneration of the tendon-bone insertion by reducing reactive oxygen species (ROS) levels and shifting macrophage polarization from M1 to M2. Additionally, DMN/PLGA@Dia improves functional recovery, as evidenced by biomechanical and gait analyses. These findings suggest that DMN/PLGA@Dia is capable of promoting tendon-bone insertion repair by alleviating oxidative stress and regulating the immune microenvironment strategies. Simple DMN/PLGA@Dia may be an effective and safe nanomedicine delivery system for tendon-bone insertion repair.