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Submitted: 25 Jun 2024
Revision: 03 Jan 2025
Accepted: 03 Feb 2025
ePublished: 12 Feb 2025
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Adv Pharm Bull. 2025;15(1): 107-122.
doi: 10.34172/apb.43295
  Abstract View: 186
  PDF Download: 28

Original Article

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

Samaneh Siapoush 1,2 ORCID logo, Mohammad Rahmati 1,3* ORCID logo, Morteza Milani 1,4, Behzad Hatami 5, Nosratollah Zarghami 1,3,6, Abbas Ebrahimi-Kalan 7, Mohammad Reza Zali 5, Kaveh Baghaei 2,5* ORCID logo

1 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6 Department of Medical biochemistry, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey.
7 Department of Neurosciences and Cognition, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Authors: Mohammad Rahmati, Email: rahmatibio@gmail.com; Kaveh Baghaei, Email: kavehbaghai@gmail.com

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 nanoparticles (NPs) targeted with vitamin A. The characterization of NPs was approved with Fourier-transform infrared (FT-IR), dynamic light scattering (DLS), and scanning electron microscopy (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 BTZ‘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, X-ray diffraction (XRD) and FT-IR showed that the size of NPs was optimum and drug was entrapped 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 nuclear factor-kappa B (NF-κB) genes suppressed in mice treated with NPs entrapped BTZ . 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 BTZ .

Conclusion: BTZ, in low amounts entrapped in targeted NPc, could ameliorate the fibrotic index in mice models.


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