Limits...
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

In vivo antitumor efficacy in tumor-bearing Kunming mice treated with Taxol® (10 mg/kg), PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) (n=5).Notes: (A) Relative tumor growth ratio (*P,0.05), (B) tumor weight, (C) images of tumor tissues, (D) relative body weight and (E) HE staining assay of the tumor sections.Abbreviations: PTX, paclitaxel; NP, nanoparticles; HE, hematoxylin and eosin.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4548758&req=5

f10-ijn-10-5219: In vivo antitumor efficacy in tumor-bearing Kunming mice treated with Taxol® (10 mg/kg), PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) (n=5).Notes: (A) Relative tumor growth ratio (*P,0.05), (B) tumor weight, (C) images of tumor tissues, (D) relative body weight and (E) HE staining assay of the tumor sections.Abbreviations: PTX, paclitaxel; NP, nanoparticles; HE, hematoxylin and eosin.

Mentions: The in vivo antitumor efficiency of PTX-NP5K was evaluated in tumor-bearing mice. The mice were treated every other day with saline, PTX-NP5K (10 mg/kg and 30 mg/kg), and Taxol® (10 mg/kg), respectively. Both PTX-NP5K and Taxol® demonstrated tumor growth inhibition (Figure 10A–C). Tumors of saline, Taxol®, PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) groups were 0.59±0.26 g, 0.38±0.19 g, 0.29±0.11 g, and 0.21±0.04 g, respectively. Clearly, PTX-NP5K exhibited better therapeutic efficiency than Taxol® at the dose of 10 mg/kg. The tumor inhibition rates of Taxol® and PTX-NP5K were 36.4% and 50.8%, respectively. It is also worth noting that although PTX-NP5K showed a higher therapy property than Taxol® at the dose of 10 mg/kg, their tumor-inhibition result was not statistically significant. Another noteworthy fact is that the mice treated with Taxol® at a dosage above 20 mg/kg showed apathy and died 1 hour after injection. However, for PTX-NP5K, the dosage can be higher than 30 mg/kg with the inhibition rate of 71.2%, which is 1.57-fold higher than that treated with Taxol® (10 mg/kg). These results indicate that the NP offer advantages of decreased side effects and improved drug tolerance. It may suggest that the PTX-NP5K is a promising platform for safe and efficient cancer chemotherapy. The body weight of the mice was also monitored every day. As shown in Figure 10D, no significant variations in body weight were noticed in saline and the treatment groups with PTX dose of 10 mg/kg. The hematoxylin and eosin staining was further investigated (Figure 10E). In saline group, the tumor cells were polykaryocytes with large irregular karyons, rich cytoplasm, and more nuclear division. Nuclei apoptosis and spotty necrosis was observed in the tumor section after PTX treatment. These in vivo antitumor effects proved that 4-arm-PEG5K-TPGS was a good vehicle of PTX and could improve the chemotherapeutic efficacy of PTX. This might be accounted for the reason that 4-arm-PEG5K-TPGS NP increased the local accumulation concentration of PTX in the tumor tissue.


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)

In vivo antitumor efficacy in tumor-bearing Kunming mice treated with Taxol® (10 mg/kg), PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) (n=5).Notes: (A) Relative tumor growth ratio (*P,0.05), (B) tumor weight, (C) images of tumor tissues, (D) relative body weight and (E) HE staining assay of the tumor sections.Abbreviations: PTX, paclitaxel; NP, nanoparticles; HE, hematoxylin and eosin.
© Copyright Policy
Related In: Results  -  Collection

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

f10-ijn-10-5219: In vivo antitumor efficacy in tumor-bearing Kunming mice treated with Taxol® (10 mg/kg), PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) (n=5).Notes: (A) Relative tumor growth ratio (*P,0.05), (B) tumor weight, (C) images of tumor tissues, (D) relative body weight and (E) HE staining assay of the tumor sections.Abbreviations: PTX, paclitaxel; NP, nanoparticles; HE, hematoxylin and eosin.
Mentions: The in vivo antitumor efficiency of PTX-NP5K was evaluated in tumor-bearing mice. The mice were treated every other day with saline, PTX-NP5K (10 mg/kg and 30 mg/kg), and Taxol® (10 mg/kg), respectively. Both PTX-NP5K and Taxol® demonstrated tumor growth inhibition (Figure 10A–C). Tumors of saline, Taxol®, PTX-NP5K (10 mg/kg), and PTX-NP5K (30 mg/kg) groups were 0.59±0.26 g, 0.38±0.19 g, 0.29±0.11 g, and 0.21±0.04 g, respectively. Clearly, PTX-NP5K exhibited better therapeutic efficiency than Taxol® at the dose of 10 mg/kg. The tumor inhibition rates of Taxol® and PTX-NP5K were 36.4% and 50.8%, respectively. It is also worth noting that although PTX-NP5K showed a higher therapy property than Taxol® at the dose of 10 mg/kg, their tumor-inhibition result was not statistically significant. Another noteworthy fact is that the mice treated with Taxol® at a dosage above 20 mg/kg showed apathy and died 1 hour after injection. However, for PTX-NP5K, the dosage can be higher than 30 mg/kg with the inhibition rate of 71.2%, which is 1.57-fold higher than that treated with Taxol® (10 mg/kg). These results indicate that the NP offer advantages of decreased side effects and improved drug tolerance. It may suggest that the PTX-NP5K is a promising platform for safe and efficient cancer chemotherapy. The body weight of the mice was also monitored every day. As shown in Figure 10D, no significant variations in body weight were noticed in saline and the treatment groups with PTX dose of 10 mg/kg. The hematoxylin and eosin staining was further investigated (Figure 10E). In saline group, the tumor cells were polykaryocytes with large irregular karyons, rich cytoplasm, and more nuclear division. Nuclei apoptosis and spotty necrosis was observed in the tumor section after PTX treatment. These in vivo antitumor effects proved that 4-arm-PEG5K-TPGS was a good vehicle of PTX and could improve the chemotherapeutic efficacy of PTX. This might be accounted for the reason that 4-arm-PEG5K-TPGS NP increased the local accumulation concentration of PTX in the tumor tissue.

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