Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes
This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosp...
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doaj-169d5787b49541ddaf6730dd07f8576e2020-11-25T00:45:15ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762019-07-01144391404Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomesShu Han0Ruiyang Sun1Hong Su2Jing Lv3Huan Xu4Di Zhang5Yuanshan Fu6Department of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, ChinaDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, ChinaDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, ChinaDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, ChinaDepartment of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China; Corresponding author. Department of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China. Tel.: +86 411 82158319.Department of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, ChinaDepartment of Anatomy, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; Corresponding author. Department of Anatomy, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China. Tel.: +86 411 86110355.This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 (P < 0.01). Conversely, for PEGylated C6 liposomes (PEG-C6-L) and conventional C6 liposomes (C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes (DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-L significantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system. Keywords: d-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate, Liposomes, pH-sensitive, PEGylationhttp://www.sciencedirect.com/science/article/pii/S1818087617309509 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shu Han Ruiyang Sun Hong Su Jing Lv Huan Xu Di Zhang Yuanshan Fu |
spellingShingle |
Shu Han Ruiyang Sun Hong Su Jing Lv Huan Xu Di Zhang Yuanshan Fu Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes Asian Journal of Pharmaceutical Sciences |
author_facet |
Shu Han Ruiyang Sun Hong Su Jing Lv Huan Xu Di Zhang Yuanshan Fu |
author_sort |
Shu Han |
title |
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes |
title_short |
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes |
title_full |
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes |
title_fullStr |
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes |
title_full_unstemmed |
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes |
title_sort |
delivery of docetaxel using ph-sensitive liposomes based on d-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: comparison with pegylated liposomes |
publisher |
Elsevier |
series |
Asian Journal of Pharmaceutical Sciences |
issn |
1818-0876 |
publishDate |
2019-07-01 |
description |
This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 (P < 0.01). Conversely, for PEGylated C6 liposomes (PEG-C6-L) and conventional C6 liposomes (C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes (DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-L significantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system. Keywords: d-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate, Liposomes, pH-sensitive, PEGylation |
url |
http://www.sciencedirect.com/science/article/pii/S1818087617309509 |
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