Enhanced intracellular accumulation and cytotoxicity of bortezomib against liver cancer cells using N-stearyl lactobionamide surface modified solid lipid nanoparticles
Copyright © 2023 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:649 |
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| Enthalten in: |
International journal of pharmaceutics - 649(2023) vom: 05. Jan., Seite 123635 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mostafaei, Farid [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.12.2023 Date Revised 20.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.123635 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Asialoglycoprotein receptors | |
| 650 | 4 | |a Bortezomib | |
| 650 | 4 | |a Galactosylated solid lipid nanoparticles | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Lactobionic acid | |
| 650 | 4 | |a Targeted drug delivery | |
| 650 | 7 | |a Bortezomib |2 NLM | |
| 650 | 7 | |a 69G8BD63PP |2 NLM | |
| 650 | 7 | |a Lipid Nanoparticles |2 NLM | |
| 650 | 7 | |a lactobionamide |2 NLM | |
| 650 | 7 | |a Drug Carriers |2 NLM | |
| 700 | 1 | |a Hemmati, Salar |e verfasserin |4 aut | |
| 700 | 1 | |a Valizadeh, Hadi |e verfasserin |4 aut | |
| 700 | 1 | |a Mahmoudian, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Sarfraz, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Abdi, Mahdieh |e verfasserin |4 aut | |
| 700 | 1 | |a Torabi, Shukoofeh |e verfasserin |4 aut | |
| 700 | 1 | |a Baradaran, Behzad |e verfasserin |4 aut | |
| 700 | 1 | |a Vosough, Massoud |e verfasserin |4 aut | |
| 700 | 1 | |a Zakeri-Milani, Parvin |e verfasserin |4 aut | |
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