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Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.

Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L - Int J Nanomedicine (2015)

Bottom Line: The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs.Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice.In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China.

ABSTRACT
Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

No MeSH data available.


Related in: MedlinePlus

In vitro release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
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f8-ijn-10-2461: In vitro release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.

Mentions: Figure 8 illustrates the in vitro drug release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs in PBS buffer (pH 7.4) supplemented with 0.1% w/v Tween 80 in the first 15 days, which exhibited biphasic release patterns. It could be observed from Figure 8 that the release of genistein from the drug-loaded PCL NPs and TPGS-b-PCL NPs showed an initial burst of 11.97% and 14.58%, respectively, in the 1st day. In the following days, the cumulative release of genistein persistently increased. After 15 days’ incubation, the cumulative release of genistein was 48.95% for PCL NPs and 58.84% for TPGS-b-PCL NPs. It could be easily concluded that TPGS-b-PCL NPs exhibited a much faster drug release than did PCL NPs. This is probably because of the hydrophilic part of the TPGS, which promotes the uptake and permeation of PBS buffer into the core of NPs to facilitate drug release.


Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.

Zhang H, Liu G, Zeng X, Wu Y, Yang C, Mei L, Wang Z, Huang L - Int J Nanomedicine (2015)

In vitro release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383221&req=5

f8-ijn-10-2461: In vitro release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs.Abbreviations: NPs, nanoparticles; PCL, poly(ε-caprolactone); TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate.
Mentions: Figure 8 illustrates the in vitro drug release profiles of genistein-loaded PCL NPs and TPGS-b-PCL NPs in PBS buffer (pH 7.4) supplemented with 0.1% w/v Tween 80 in the first 15 days, which exhibited biphasic release patterns. It could be observed from Figure 8 that the release of genistein from the drug-loaded PCL NPs and TPGS-b-PCL NPs showed an initial burst of 11.97% and 14.58%, respectively, in the 1st day. In the following days, the cumulative release of genistein persistently increased. After 15 days’ incubation, the cumulative release of genistein was 48.95% for PCL NPs and 58.84% for TPGS-b-PCL NPs. It could be easily concluded that TPGS-b-PCL NPs exhibited a much faster drug release than did PCL NPs. This is probably because of the hydrophilic part of the TPGS, which promotes the uptake and permeation of PBS buffer into the core of NPs to facilitate drug release.

Bottom Line: The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs.Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice.In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China.

ABSTRACT
Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

No MeSH data available.


Related in: MedlinePlus