Enhanced intracellular accumulation and cytotoxicity of bortezomib against liver cancer cells using N-stearyl lactobionamide surface modified solid lipid nanoparticles.

Autor: Mostafaei F; Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran., Hemmati S; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Valizadeh H; Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Mahmoudian M; Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran., Sarfraz M; College of Pharmacy, Al Ain University, Al Ain, United Arab Emirates., Abdi M; Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran., Torabi S; Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran., Baradaran B; Immunology Research Center and Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Vosough M; Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital-Huddinge, Sweden., Zakeri-Milani P; Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: parvinzm@gmail.com.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jan 05; Vol. 649, pp. 123635. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1016/j.ijpharm.2023.123635
Abstrakt: Asialoglycoprotein receptors (ASGPRs) are highly expressed on hepatocytes and have been used for liver-targeted delivery and hepatocellular carcinoma (HCC) therapy. However, targeted delivery of bortezomib (BTZ) to HCC has not been reported. In this study, N-stearyl lactobionamide (N-SALB) with galactose (Gal) moiety was synthesized as a targeting agent and its structure was confirmed by FT-IR and NMR analyses. N-SALB surface-modified solid lipid nanoparticles (SLNs) loaded with BTZ (Gal-SLNs/BTZ) were developed to target BTZ delivery into HCC cancer cells. The Gal-SLNs/BTZ had an average particle size of 116.3 nm, polydispersity index (PDI) of 0.210, and zeta potential of -13.8 mV. TEM analysis showed their nanometer-sized spherical morphology. The encapsulation efficiency (EE) and drug loading (DL) capacity were 84.5 % and 1.16 %, respectively. Release studies showed that BTZ loaded inside the SLNs was slowly released over a period of 72 h at pH 7.4. Flow cytometry analysis showed significantly higher intracellular uptake of N-SALB-targeted nanoparticles than non-targeted nanoparticles in HepG2 cells. All lipid formulations showed good biocompatibility in the cytotoxicity study using MTT assay. Concentration-dependent cytotoxicity was observed for all formulations, with N-SALB-targeted nanoparticles demonstrating more cytotoxicity against HepG2 cells. The highest percentage of apoptosis was obtained for N-SALB-targeted nanoparticles compared to non-targeted nanoparticles (42.2 % and 8.70 %, respectively). Finally, biodistribution studies in HepG2 bearing nude mice showed that the accumulation of targeted nanoparticles in the tumor was significantly higher than non-targeted nanoparticles.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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