Tendinitis is a tendon disorder related to inflammation
and pain,
due to an injury or overuse of the tissue, which is hypocellular and
hypovascular, leading to limited repair which occurs in a disorganized
deposition of extracellular matrix that leads to scar formation and
fibrosis, ultimately resulting in impaired tendon integrity. Current
conventional treatments are limited and often ineffective, highlighting
the need for new therapeutic strategies. In this work, acetalated-dextran
nanoparticles (AcDEX NPs) loaded with curcumin and coated with tannic
acid (TA) are developed to exploit the anti-inflammatory and anti-fibrotic
properties of the two compounds. For this purpose, a microfluidic
technique was used in order to obtain particles with a precise size
distribution, aiming to decrease the batch-to-batch variability for
possible future clinical translation. Coating with TA increased not
only the stability of the nanosystem in different media but also enhanced
the interaction and the cell-uptake in primary human tenocytes and
KG-1 macrophages. The nanosystem exhibited good biocompatibility toward
these cell types and a good release profile in an inflammatory environment.
The efficacy was demonstrated by real-time quantitative polymerase
chain reaction, in which the curcumin loaded in the particles showed
good anti-inflammatory properties by decreasing the expression of
NF-κb and TA-coated NPs showing anti-fibrotic effect, decreasing
the gene expression of TGF-β. Overall, due to the loading of
curcumin and TA in the AcDEX NPs, and their synergistic activity,
this nanosystem has promising properties for future application in
tendinitis.