Skip to main content

Advertisement

SpringerLink
Log in

Efficiency and mechanism of intracellular paclitaxel delivery by novel nanopolymer-based tumor-targeted delivery system, NanoxelTM

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Introduction

An increasing research interest has been directed toward nanoparticle-based drug delivery systems for their advantages. The appropriate amalgamation of pH sensitivity and tumor targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity.

Materials and Methods

A novel pH sensitive Cremophor-free paclitaxel formulation, NanoxelTM, was developed in which the drug is delivered as nanomicelles using a polymeric carrier that specifically targets tumors. The efficiency and mechanism of intracellular paclitaxel delivery by NanoxelTM was compared with two other commercially available paclitaxel formulations: AbraxaneTM and IntaxelTM, using different cell lines representing target cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission electron microscopy and quantitative intracellular paclitaxel measurements by high performance liquid chromatography.

Results

The data obtained from the present study revealed that the uptake of nanoparticle-based formulations NanoxelTM and AbraxaneTM is mediated by the process of endocytosis and the uptake of paclitaxel was remarkably superior to IntaxelTM in all cell lines tested. Moreover, the intracellular uptake of paclitaxel in NanoxelTM- and AbraxaneTM-treated groups was comparable. Hence, the nanoparticle-based formulations of paclitaxel (NanoxelTM and AbraxaneTM) are endowed with higher efficiency to deliver the drug to target cells as compared to the conventional Cremophor-based formulation.

Conclusion

NanoxelTM appears to be of great promise in tumor targeting and may provide an advantage for paclitaxel delivery into cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mo Y, Lim LY (2005) Paclitaxel-loaded PLGA nanoparticles: potentiation of anticancer activity by surface conjugation with wheat germ agglutinin. J Control Release 108(2–3):244–262

    Article  PubMed  CAS  Google Scholar 

  2. Ebbesen M, Jensen TG (2006) Nanomedicine: techniques, potentials, and ethical implications. J Biomed Biotechnol 2006(5):51516

    PubMed  Google Scholar 

  3. Gelderblom H, Verweij J, Nooter K, Sparreboom A, Cremophor EL (2001) The drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37(13):1590–1598

    Article  PubMed  CAS  Google Scholar 

  4. Kloover JS, Den Bakker MA, Gelderblom H, van Meerbeeck JP (2004) Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens. Br J Cancer 90(2):304–305

    Article  PubMed  CAS  Google Scholar 

  5. Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, Brem H (2007) Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf 6(5):609–621

    Article  PubMed  CAS  Google Scholar 

  6. Skwarczynski M, Hayashi Y, Kiso Y (2006) Paclitaxel prodrugs: toward smarter delivery of anticancer agents. J Med Chem 49(25):7253–7269

    Article  PubMed  CAS  Google Scholar 

  7. Brahmachari BH, Hazra A, Majumdar A (2011) Adverse drug reaction profile of nanoparticle versus conventional formulation of paclitaxel: an observational study. Indian J Pharmacol. 43(2):126–130

    Article  PubMed  CAS  Google Scholar 

  8. Charoentum C, Thongprasert S, Chewasakulyong B (2007) Phase II study of 24-hour infusion of paclitaxel (Intaxel) with carboplatin in advanced non-small cell lung cancer. Gan To Kagaku Ryoho 34(10):1603–1607

    PubMed  CAS  Google Scholar 

  9. Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A et al (2006) Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res Off J Am Assoc Cancer Res 12(4):1317–1324

    Article  CAS  Google Scholar 

  10. Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, Yang A et al (2005) Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol) Clin Cancer Res 11(11):4136–4143

    Article  PubMed  CAS  Google Scholar 

  11. Fader AN, Rose PG (2009) Abraxane for the treatment of gynecologic cancer patients with severe hypersensitivity reactions to paclitaxel. Int J Gynecol Cancer 19(7):1281–1283

    Article  PubMed  Google Scholar 

  12. Feng T, Szabo E, Dziak E, Opas M (2010) Cytoskeletal disassembly and cell rounding promotes adipogenesis from ES cells. Stem Cell Rev 6(1):74–85

    Google Scholar 

  13. Petrelli F, Borgonovo K, Barni S (2010) Targeted delivery for breast cancer therapy: the history of nanoparticle–albumin-bound paclitaxel. Expert Opin Pharmacother 11(8):1413–1432

    Google Scholar 

  14. Sun X, Yan Y, Liu S, Cao Q, Yang M, Neamati N, et al (2011) 18F-FPPRGD2 and 18F-FDG PET of response to Abraxane therapy. J Nucl Med 52(1):140–146

    Google Scholar 

  15. Huh JW, Kim HR (2009) Postoperative chemotherapy after neoadjuvant chemoradiation and surgery for rectal cancer: is it essential for patients with ypT0-2N0? J Surg Oncol 100(5):387–391

    Article  PubMed  CAS  Google Scholar 

  16. van Vlerken LE, Amiji MM (2006) Multi-functional polymeric nanoparticles for tumour-targeted drug delivery. Expert Opin Drug Deliv 3(2):205–216

    Article  PubMed  Google Scholar 

  17. Wang SH, Lee CW, Chiou A, Wei PK (2010) Size-dependent endocytosis of gold nanoparticles studied by three-dimensional mapping of plasmonic scattering images. J Nanobiotechnology 8:33

    Google Scholar 

  18. Jin C, Bai L, Wu H, Tian F, Guo G (2007) Radiosensitization of paclitaxel, etanidazole and paclitaxel + etanidazole nanoparticles on hypoxic human tumor cells in vitro. Biomaterials 28(25):3724–3730

    Article  PubMed  CAS  Google Scholar 

  19. Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37(13):1590–1598

    Article  PubMed  CAS  Google Scholar 

  20. Liaudet L, Soriano FG, Szabo C (2000) Biology of nitric oxide signaling. Crit Care Med 28(4 Suppl):N37–N52

    Article  PubMed  CAS  Google Scholar 

  21. Jang SH, Wientjes MG, Lu D, Au JL (2003) Drug delivery and transport to solid tumors. Pharm Res 20(9):1337–1350

    Article  PubMed  CAS  Google Scholar 

  22. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407(6801):249

    Article  PubMed  CAS  Google Scholar 

  23. Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res Official J Am Assoc Cancer Res 14(5):1310–1316

    Article  CAS  Google Scholar 

  24. Singh AT, Jaggi M, Khattar D, Awasthi A, Mishra SK, Tyagi S et al (2008) A novel nanopolymer based tumor targeted delivery system for paclitaxel. J Clin Oncol 26(May 20 suppl; abstr 11095)

Download references

Acknowledgments

This study has been presented in the poster form in The European Multidisciplinary Cancer Congress, 2011, Stockholm.

Conflict of interest

This project was financially supported by Fresenius Kabi. Dr. Hrishikesh Kulkarni, Dr. Sadanand Kulkarni and Dr. Shiva Kant Mishra are employees of Fresenius Kabi.

Author information

Authors and Affiliations

  1. Dabur Research Foundations, 22, Site IV, Sahibabad, Ghaziabad, 201010, Uttar Pradesh, India

    Alka Madaan, Pratibha Singh, Anshumali Awasthi, Ritu Verma, Anu T. Singh & Manu Jaggi

  2. Fresenius Kabi Asia Pacific Limited, 50/F Sun Hung Kai Centre, 30 Harbour Road, Wanchai, Hong Kong

    Hrishikesh Kulkarni

  3. Medical Affairs and Clinical Research, Fresenius Kabi India Private Limited, Echelon Institutional Area, Plot No 11, Sector 32, Gurgaon, 121001, Haryana, India

    Shiva Kant Mishra & Sadanand Kulkarni

Authors
  1. Alka Madaan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pratibha Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anshumali Awasthi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ritu Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anu T. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manu Jaggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiva Kant Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sadanand Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hrishikesh Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hrishikesh Kulkarni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Madaan, A., Singh, P., Awasthi, A. et al. Efficiency and mechanism of intracellular paclitaxel delivery by novel nanopolymer-based tumor-targeted delivery system, NanoxelTM . Clin Transl Oncol 15, 26–32 (2013). https://doi.org/10.1007/s12094-012-0883-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-012-0883-2

Keywords

Search

Navigation