Macrophage-targeted mannose-decorated PLGA-vegetable oil hybrid nanoparticles loaded with anti-inflammatory agents

Abstract

This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quantitative investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake respectively improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.