Macrophages play a key role in the development of many diseases, like tissue injury, cancer, and autoimmune diseases. So far, single‐drug loaded nanoparticles are developed to target macrophages. Nevertheless, macrophage dysregulation can induce multiple conditions, i.e., inflammation and fibrosis. Therefore, the simultaneous codelivery of a small molecule drug and a small interfering RNA (siRNA) for gene silencing may be beneficial to modulate macrophage dysfunction. Herein, hybrid lipid–polymer nanoparticles (LPNs) coloaded with both budesonide and enhanced green fluorescence protein siRNA (eGFP‐siRNA) as model anti‐inflammatory small molecule drug and siRNA, respectively, are developed by an optimized microfluidics method. Specifically, a poly(lactic‐co‐glycolic acid) core is coated by a lipid shell, and LPNs with size homogeneity and colloidal stability are obtained. Both payloads are loaded efficiently, and a controlled release is achieved. Additionally, LPNs are nontoxic in murine RAW 264.7 cells and human THP‐1 cells and are efficiently taken up by these cells. Finally, the transfection efficiency of dual‐loaded LPNs is high at low LPNs doses, thus proving the suitability of this nanosystem for gene silencing. Overall, the optimized LPNs are a suitable nanoplatform for the dual drug delivery to macrophages for the treatment of complex conditions requiring dual therapeutic approaches.

Microfluidic on-chip production of polymeric hydrogel microspheres (MPs) can be designed for the loading of different biologically active cargos and living cells. Despite the different gelation strategies, internal gelation methods...

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 TAcoated 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.