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 |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:588 |
|---|---|
| Enthalten in: |
International journal of pharmaceutics - 588(2020) vom: 15. Okt., Seite 119799 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Ruoning [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.06.2021 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ijpharm.2020.119799 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM314026053 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM314026053 | ||
| 003 | DE-627 | ||
| 005 | 20231225151836.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ijpharm.2020.119799 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1046.xml |
| 035 | |a (DE-627)NLM314026053 | ||
| 035 | |a (NLM)32828973 | ||
| 035 | |a (PII)S0378-5173(20)30784-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Ruoning |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impacts of particle size on the cytotoxicity, cellular internalization, pharmacokinetics and biodistribution of betulinic acid nanosuspensions in combined chemotherapy |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.06.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 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 | |
| 650 | 4 | |a Different particle sizes | |
| 650 | 7 | |a Pentacyclic Triterpenes |2 NLM | |
| 650 | 7 | |a Triterpenes |2 NLM | |
| 650 | 7 | |a Betulinic Acid |2 NLM | |
| 650 | 7 | |a 4G6A18707N |2 NLM | |
| 700 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 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 | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of pharmaceutics |d 1992 |g 588(2020) vom: 15. Okt., Seite 119799 |w (DE-627)NLM07779785X |x 1873-3476 |7 nnns |
| 773 | 1 | 8 | |g volume:588 |g year:2020 |g day:15 |g month:10 |g pages:119799 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ijpharm.2020.119799 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 588 |j 2020 |b 15 |c 10 |h 119799 | ||