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D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery.

Wu Y, Chu Q, Tan S, Zhuang X, Bao Y, Wu T, Zhang Z - Int J Nanomedicine (2015)

Bottom Line: Paclitaxel (PTX) is one of the most effective antineoplastic drugs.Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG(5K)-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780), non-small cell lung cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells.More importantly, PTX-loaded 4-arm-PEG(5K)-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol(®) in S180 sarcoma-bearing mice models.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Paclitaxel (PTX) is one of the most effective antineoplastic drugs. Its current clinical administration Taxol(®) is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP) with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS) and 4-arm-polyethylene glycol (4-arm-PEG) with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG(5K)-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG(5K)-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780), non-small cell lung cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG(5K)-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol(®) in S180 sarcoma-bearing mice models. This study suggested that 4-arm-PEG(5K)-TPGS NP may have the potential as an anticancer drug delivery system.

No MeSH data available.


Related in: MedlinePlus

Cellular uptake of coumarin-6-NP5K by A2780 cells.Notes: (A) CLSM images after 2 hours incubation and (B) MFI value analyzed by flow cytometry.Abbreviations: NP, nanoparticles; CLSM, confocal laser scanning microscopy; MFI, mean fluorescence intensity; DAPI, 4′,6-diamidino-2-phenylindole.
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f6-ijn-10-5219: Cellular uptake of coumarin-6-NP5K by A2780 cells.Notes: (A) CLSM images after 2 hours incubation and (B) MFI value analyzed by flow cytometry.Abbreviations: NP, nanoparticles; CLSM, confocal laser scanning microscopy; MFI, mean fluorescence intensity; DAPI, 4′,6-diamidino-2-phenylindole.

Mentions: It is known that many anticancer drugs including PTX take therapeutic effects only inside the tumor cells. Accordingly, the cellular uptake of coumarin-6-NP5K was qualitatively analyzed on A2780 cells by CLSM. After 2 hours incubation, NP (green) were intensively located around the nuclei (blue) (Figure 6A), which suggested the effective uptake of the NP by the cells.


D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery.

Wu Y, Chu Q, Tan S, Zhuang X, Bao Y, Wu T, Zhang Z - Int J Nanomedicine (2015)

Cellular uptake of coumarin-6-NP5K by A2780 cells.Notes: (A) CLSM images after 2 hours incubation and (B) MFI value analyzed by flow cytometry.Abbreviations: NP, nanoparticles; CLSM, confocal laser scanning microscopy; MFI, mean fluorescence intensity; DAPI, 4′,6-diamidino-2-phenylindole.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548758&req=5

f6-ijn-10-5219: Cellular uptake of coumarin-6-NP5K by A2780 cells.Notes: (A) CLSM images after 2 hours incubation and (B) MFI value analyzed by flow cytometry.Abbreviations: NP, nanoparticles; CLSM, confocal laser scanning microscopy; MFI, mean fluorescence intensity; DAPI, 4′,6-diamidino-2-phenylindole.
Mentions: It is known that many anticancer drugs including PTX take therapeutic effects only inside the tumor cells. Accordingly, the cellular uptake of coumarin-6-NP5K was qualitatively analyzed on A2780 cells by CLSM. After 2 hours incubation, NP (green) were intensively located around the nuclei (blue) (Figure 6A), which suggested the effective uptake of the NP by the cells.

Bottom Line: Paclitaxel (PTX) is one of the most effective antineoplastic drugs.Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG(5K)-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780), non-small cell lung cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells.More importantly, PTX-loaded 4-arm-PEG(5K)-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol(®) in S180 sarcoma-bearing mice models.

View Article: PubMed Central - PubMed

Affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Paclitaxel (PTX) is one of the most effective antineoplastic drugs. Its current clinical administration Taxol(®) is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP) with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS) and 4-arm-polyethylene glycol (4-arm-PEG) with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG(5K)-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG(5K)-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780), non-small cell lung cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG(5K)-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol(®) in S180 sarcoma-bearing mice models. This study suggested that 4-arm-PEG(5K)-TPGS NP may have the potential as an anticancer drug delivery system.

No MeSH data available.


Related in: MedlinePlus