Development of siRNA and Budesonide Dual‐Loaded Hybrid Lipid–Polymer Nanoparticles by Microfluidics Technology as a Platform for Dual Drug Delivery to Macrophages: An In Vitro Mechanistic Study

Abstract

AbstractMacrophages 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.