L-carnitine modified nanoparticles target the OCTN2 transporter to improve the oral absorption of jujuboside B
Copyright © 2024 Elsevier B.V. All rights reserved..
As a bioactive saponin derived from the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, jujuboside B (JuB) shows great potential in anti-anxiety, anti-depression and improving learning and memory function. However, its oral bioavailability is very poor. In this study, a novel drug-loading nanoparticles system was prepared with polyethylene glycol and polylactic-co-glycolic acid copolymer (PEG-PLGA), and further modified with L-carnitine (LC) to target intestinal organic cation/carnitine transporter 2 (OCTN2) to improve the oral absorption of JuB. Under the optimized preparation conditions, the particle sizes of obtained JuB-PEG-PLGA nanoparticles (B-NPs) and LC modified B-NPs (LC-B-NPs) were 110.67 ± 11.37 nm and 134.00 ± 2.00 nm with the entrapment efficiency (EE%) 73.46 ± 1.26 % and 76.01 ± 2.10 %, respectively. The pharmacokinetics in SD rats showed that B-NPs and LC-B-NPs increased the bioavailability of JuB to 134.33 % and 159.04 % respectively. In Caco-2 cell model, the prepared nanoparticles significantly increased cell uptake of JuB, which verified the pharmacokinetic results. The absorption of LC-B-NPs mainly depended on OCTN2 transporter, and Na+ played an important role. Caveolin and clathrin were involved in the endocytosis of the two nanoparticles. In conclusion, both B-NPs and LC-B-NPs can improve the oral absorption of JuB, and the modification of LC can effectively target the OCTN2 transporter.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:196 |
|---|---|
| Enthalten in: |
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 196(2024) vom: 01. Feb., Seite 114185 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Wei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3WJQ0SDW1A |
|---|
| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 19.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejpb.2024.114185 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367708817 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367708817 | ||
| 003 | DE-627 | ||
| 005 | 20240219232022.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240128s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejpb.2024.114185 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1299.xml |
| 035 | |a (DE-627)NLM367708817 | ||
| 035 | |a (NLM)38280469 | ||
| 035 | |a (PII)S0939-6411(24)00011-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Wei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a L-carnitine modified nanoparticles target the OCTN2 transporter to improve the oral absorption of jujuboside B |
| 264 | 1 | |c 2024 | |
| 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 19.02.2024 | ||
| 500 | |a Date Revised 19.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a As a bioactive saponin derived from the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, jujuboside B (JuB) shows great potential in anti-anxiety, anti-depression and improving learning and memory function. However, its oral bioavailability is very poor. In this study, a novel drug-loading nanoparticles system was prepared with polyethylene glycol and polylactic-co-glycolic acid copolymer (PEG-PLGA), and further modified with L-carnitine (LC) to target intestinal organic cation/carnitine transporter 2 (OCTN2) to improve the oral absorption of JuB. Under the optimized preparation conditions, the particle sizes of obtained JuB-PEG-PLGA nanoparticles (B-NPs) and LC modified B-NPs (LC-B-NPs) were 110.67 ± 11.37 nm and 134.00 ± 2.00 nm with the entrapment efficiency (EE%) 73.46 ± 1.26 % and 76.01 ± 2.10 %, respectively. The pharmacokinetics in SD rats showed that B-NPs and LC-B-NPs increased the bioavailability of JuB to 134.33 % and 159.04 % respectively. In Caco-2 cell model, the prepared nanoparticles significantly increased cell uptake of JuB, which verified the pharmacokinetic results. The absorption of LC-B-NPs mainly depended on OCTN2 transporter, and Na+ played an important role. Caveolin and clathrin were involved in the endocytosis of the two nanoparticles. In conclusion, both B-NPs and LC-B-NPs can improve the oral absorption of JuB, and the modification of LC can effectively target the OCTN2 transporter | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Jujuboside B | |
| 650 | 4 | |a L-carnitine | |
| 650 | 4 | |a Nanoparticles | |
| 650 | 4 | |a OCTN2 | |
| 650 | 4 | |a Oral bioavailability | |
| 650 | 7 | |a polyethylene glycol-poly(lactide-co-glycolide) |2 NLM | |
| 650 | 7 | |a jujuboside B |2 NLM | |
| 650 | 7 | |a Carnitine |2 NLM | |
| 650 | 7 | |a S7UI8SM58A |2 NLM | |
| 650 | 7 | |a Saponins |2 NLM | |
| 650 | 7 | |a Polyesters |2 NLM | |
| 650 | 7 | |a Polyethylene Glycols |2 NLM | |
| 650 | 7 | |a 3WJQ0SDW1A |2 NLM | |
| 700 | 1 | |a Zhang, Yanqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Junbo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V |d 1997 |g 196(2024) vom: 01. Feb., Seite 114185 |w (DE-627)NLM090658442 |x 1873-3441 |7 nnns |
| 773 | 1 | 8 | |g volume:196 |g year:2024 |g day:01 |g month:02 |g pages:114185 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejpb.2024.114185 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 196 |j 2024 |b 01 |c 02 |h 114185 | ||