Enhanced paracellular and transcellular paclitaxel permeation by chitosan–vitamin E succinate–N-acetyl-l-cysteine copolymer on Caco-2 cell monolayer
The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate– N -acetyl- l -cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric na...
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Published in | Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 16; no. 4; pp. 1 - 16 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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01.04.2014
Springer Springer Nature B.V |
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Abstract | The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate–
N
-acetyl-
l
-cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS–VES–NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS–VES–NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS–VES–NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly,
P
app
value of PTX-loaded CS–VES–NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS–VES–NAC copolymer, the
P
app
value of PTX was almost increased up to 19.5-fold. All the results indicate that CS–VES–NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation. |
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AbstractList | The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate-N-acetyl-l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P ^sub app^ value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P ^sub app^ value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.[PUBLICATION ABSTRACT] The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate-N-acetyl-l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P sub(app) value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P sub(app) value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation. The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan–vitamin E succinate– N -acetyl- l -cysteine (CS–VES–NAC) nanomicelles from the cellular level. In aqueous solution, CS–VES–NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS–VES–NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS–VES–NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS–VES–NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS–VES–NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS–VES–NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS–VES–NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation. |
ArticleNumber | 2355 |
Author | Tang, Yilin Sun, Jin Pu, Xiaohui Zhang, Youxi He, Zhonggui Lian, He Zhang, Tianhong |
Author_xml | – sequence: 1 givenname: He surname: Lian fullname: Lian, He organization: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University – sequence: 2 givenname: Tianhong surname: Zhang fullname: Zhang, Tianhong email: pharmazhang@163.com organization: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University – sequence: 3 givenname: Jin surname: Sun fullname: Sun, Jin organization: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research – sequence: 4 givenname: Xiaohui surname: Pu fullname: Pu, Xiaohui organization: Department of Pharmaceutical Analysis, School of Pharmacy, Henan University – sequence: 5 givenname: Yilin surname: Tang fullname: Tang, Yilin organization: School of Material Science and Engineering, Xi’an Jiaotong University – sequence: 6 givenname: Youxi surname: Zhang fullname: Zhang, Youxi organization: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University – sequence: 7 givenname: Zhonggui surname: He fullname: He, Zhonggui email: hezhonggui@vip.163.com organization: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University |
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CitedBy_id | crossref_primary_10_1021_acs_molpharmaceut_6b00335 crossref_primary_10_1021_acsabm_9b00813 crossref_primary_10_1007_s10854_022_07817_6 crossref_primary_10_3390_molecules29081769 crossref_primary_10_1007_s00396_014_3429_z crossref_primary_10_1016_j_carbpol_2017_11_053 crossref_primary_10_1016_j_foodres_2022_112220 crossref_primary_10_1039_C6RA09662J crossref_primary_10_1016_j_ijbiomac_2022_09_101 |
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Keywords | Paracellular Transcellular Nanomedicine CS–VES–NAC Paclitaxel Drugs Cysteine Toxicity Cytotoxicity Confocal microscopy Drug carrier CS-VES-NAC Self-assembly Copolymers Endocytosis Aqueous solutions Monolayers Chitosan Medical application |
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Title | Enhanced paracellular and transcellular paclitaxel permeation by chitosan–vitamin E succinate–N-acetyl-l-cysteine copolymer on Caco-2 cell monolayer |
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