Impacts of particle size on the cytotoxicity, cellular internalization, pharmacokinetics and biodistribution of betulinic acid nanosuspensions in combined chemotherapy
Copyright © 2020 Elsevier B.V. All rights reserved..
To evaluate the effect of particle size on the cellular internalization, tissue distribution, and bioavailability of betulinic acid nanosuspensions (BA/NSs) and further investigate the combined effect of BA/NSs and Taxol® on breast cancer, BA/NSs with different particle sizes (160 nm, 400 nm, and 700 nm) were prepared by an efficient universal green technology. The use of BA/NS (160 nm) was more likely to increase the BA release rate and enhance bioavailability compared with the use of larger size particles. BA/NSs were internalized by 4T1 cells in different ways, including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. For the 4T1 orthotopic tumor model, BA/NS (160 nm) showed a tendency to accumulate at a higher level in tumor tissue. Moreover, combination therapy with BA/NSs and Taxol® showed remarkable potential to enhance antitumor activity in vitro and in vivo. The cytotoxicity and apoptotic ability of the different preparations decreased in the following order: BA/NS (160 nm) + Taxol®, BA/NS (400 nm) + Taxol®, and BA/NS (700 nm) + Taxol®. The tumor inhibition rates of BA/NSs (160 nm, 400 nm, and 700 nm) combined with Taxol® were 2.35-, 1.74- and 1.12-fold higher than that of free BA, respectively. The combined chemotherapy showed good safety, indicating that it had the effect of enhancing treatment and reducing toxicity.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:588 |
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Enthalten in: |
International journal of pharmaceutics - 588(2020) vom: 15. Okt., Seite 119799 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wang, Ruoning [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 17.06.2021 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.ijpharm.2020.119799 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM314026053 |
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520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
520 | |a To evaluate the effect of particle size on the cellular internalization, tissue distribution, and bioavailability of betulinic acid nanosuspensions (BA/NSs) and further investigate the combined effect of BA/NSs and Taxol® on breast cancer, BA/NSs with different particle sizes (160 nm, 400 nm, and 700 nm) were prepared by an efficient universal green technology. The use of BA/NS (160 nm) was more likely to increase the BA release rate and enhance bioavailability compared with the use of larger size particles. BA/NSs were internalized by 4T1 cells in different ways, including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. For the 4T1 orthotopic tumor model, BA/NS (160 nm) showed a tendency to accumulate at a higher level in tumor tissue. Moreover, combination therapy with BA/NSs and Taxol® showed remarkable potential to enhance antitumor activity in vitro and in vivo. The cytotoxicity and apoptotic ability of the different preparations decreased in the following order: BA/NS (160 nm) + Taxol®, BA/NS (400 nm) + Taxol®, and BA/NS (700 nm) + Taxol®. The tumor inhibition rates of BA/NSs (160 nm, 400 nm, and 700 nm) combined with Taxol® were 2.35-, 1.74- and 1.12-fold higher than that of free BA, respectively. The combined chemotherapy showed good safety, indicating that it had the effect of enhancing treatment and reducing toxicity | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Betulinic acid nanosuspensions | |
650 | 4 | |a Cellular internalization, pharmacokinetics and biodistribution | |
650 | 4 | |a Combined chemotherapy | |
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700 | 1 | |a Jia, Xiaoshun |e verfasserin |4 aut | |
700 | 1 | |a Wang, Honglan |e verfasserin |4 aut | |
700 | 1 | |a Li, Wen |e verfasserin |4 aut | |
700 | 1 | |a Li, Junsong |e verfasserin |4 aut | |
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