The aim of the work was to develop rhein loaded polymeric nanoparticles (R-PNPs). Nanoparticles were prepared by three methods, solvent emulsion-evaporation, double emulsion, and nanoprecipitation, by means of experimental design. Additionally, the effects of the best formulation on in vitro cytotoxicity and inflammation were evaluated. The solvent emulsion-evaporation method presented the highest encapsulation efficiency of the three techniques (38.41%), as well as had a mean diameter of 189.33 nm and a polydispersity index of less than 0.1. Despite efforts to optimize the encapsulation of rhein, the drug release from nanoparticles was close to 50% during the first 5 min, followed by a continuous release within 60 min. It was observed that macrophages exposed to the highest concentration of R-PNPs showed cell viability about 80% and at the lowest nanoparticle concentrations was closed to 100%. IL-1β in cell culture supernatants was decreased in the presence of R-PNPs and TNFα concentrations were lower than the sensitivity of the assay. ROS production was only inhibited with R-PNPs at concentrations of 2.5 and 5 μM. In conclusion, the solvent emulsion-evaporation was the best method evaluated to obtain nanoparticles with the desired specifications. It was possible to assess R-PNPs with low cytotoxicity and anti-inflammatory properties showed by the inhibition of IL-1β production and a low decrease in ROS production.
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