Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis

In this study, an emulsion solvent evaporation method was used to produce Eudragit RL (ERL) nanoparticles (NPs) loaded with simvastatin (SIM) for the treatment of ulcerative colitis (UC). Accordingly, the effects of different formulation variables on the properties of NPs were evaluated using the Box-Behnken design. The optimized NPs were then coated by Eudragit FS30D (EFS30D). Drug release was studied in different physiological environments. Colitis was induced by 3% of acetic acid in rats, which received NPs of SIM (10 mg/kg/day), mesalazine (150 mg/kg/day), blank NPs and normal saline orally for 5 days. Macroscopic histopathological evaluation and biochemical analysis, including myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the colon tissues, were carried out in this study. The optimized SIM-ERL NPs showed the particle size of 182.48 +/- 4.57 nm, the polydispersity index of 0.29 +/- 0.12, the zeta potential of 26.45 +/- 4.57 mV, drug loading % of 34.64 +/- 0.48, the encapsulation efficiency % of 98.68 +/- 0.69, and the release efficiency % of 35.78 +/- 1.37. Coating the optimized NPs with EFS30D caused an increase in particle size and a decrease in the zeta potential of NPs. The optimized SIM-EFS30D/RL NPs improved the macroscopic and histopathological scores. Also, MPO activity and MDA level were reduced significantly by NPs, as compared to the control group. Therefore, this drug delivery system can be an alternative to the previous treatments of UC.

Automated summary

In this study, Eudragit RL nanoparticles loaded with simvastatin were prepared using an emulsion solvent evaporation method for the treatment of ulcerative colitis. The optimized nanoparticles showed improved therapeutic effects and reduced inflammation in a rat model of colitis. This drug delivery system can be considered as an alternative treatment for ulcerative colitis.