Targeted Delivery of Bortezomib Using Retinoid-Based Nanoparticle: Modulating Liver Fibrosis through the TGF-β1/Smad3 Pathway

Abstract

Purpose: Hepatic stellate cells (HSCs) play a crucial role in fibrosis progression. we have developed a targeted delivery approach using A-functionalized nanoparticles for Bortezomib(BTZ) specifically for activated HSCs in a mouse model of liver fibrosis. Methods: The emulsion solvent evaporation method was used to form NPs targeted with Vit A. The characterization of NPs was approved with FTIR, NMR, DLS, and SEM. Also, the biodistribution of NPs inside mice bodies was conducted via fluorescent drug. the cytotoxicity of NPs evaluated in different dose in vitro test. Compared to control groups, a serological evaluation, molecular examination and protein expression were performed based on BRZ's impact on fibrotic index on model mice after treatment with targeted NPs loaded with BTZ. Results: Characterization of synthesized targeted NPs containing BTZ through DLS, XRD and FT-IR showed that the size of NPs was optimum and drug was entraped inside of NPs successfully. Biodistribution of engineered targeted nanoparticles incorporating BTZ in mice showed a gradual tendency of NPs in the liver zone. Moreover, mice treated with vitamin A-targeted containing BTZ showed decreased expression of collagen I, collagen III, and α-SMA; also, the level of expression in TGF-β1/Smad3 and NF-κB genes suppressed in mice treated with NPs entrapped Bortezomib. In line with these results, histopathologic and serological results showed significant exacerbation in non-target and drug-free nanoparticle-treated mice. The best result was seen in mice treated with targeted Bortezomib. Conclusion: Bortezomib, in low amounts entrapped in targeted NPc, could ameliorate the fibrotic index in mice models.

Keywords: Bortezomib, Proteasome inhibitor, Liver fibrosis, TGF-β1, Nanoparticles