Clinical and Translational Oncology

, Volume 15, Issue 1, pp 26–32 | Cite as

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

  • Alka Madaan
  • Pratibha Singh
  • Anshumali Awasthi
  • Ritu Verma
  • Anu T. Singh
  • Manu Jaggi
  • Shiva Kant Mishra
  • Sadanand Kulkarni
  • Hrishikesh Kulkarni
Research Article

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.

Keywords

Paclitaxel Delivery system Tumor Naoxel Nanoparticle Intaxel 

References

  1. 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):244–262PubMedCrossRefGoogle Scholar
  2. 2.
    Ebbesen M, Jensen TG (2006) Nanomedicine: techniques, potentials, and ethical implications. J Biomed Biotechnol 2006(5):51516PubMedGoogle Scholar
  3. 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):1590–1598PubMedCrossRefGoogle Scholar
  4. 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):304–305PubMedCrossRefGoogle Scholar
  5. 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):609–621PubMedCrossRefGoogle Scholar
  6. 6.
    Skwarczynski M, Hayashi Y, Kiso Y (2006) Paclitaxel prodrugs: toward smarter delivery of anticancer agents. J Med Chem 49(25):7253–7269PubMedCrossRefGoogle Scholar
  7. 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):126–130PubMedCrossRefGoogle Scholar
  8. 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):1603–1607PubMedGoogle Scholar
  9. 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):1317–1324CrossRefGoogle Scholar
  10. 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):4136–4143PubMedCrossRefGoogle Scholar
  11. 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):1281–1283PubMedCrossRefGoogle Scholar
  12. 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):74–85Google Scholar
  13. 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):1413–1432Google Scholar
  14. 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):140–146Google Scholar
  15. 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):387–391PubMedCrossRefGoogle Scholar
  16. 16.
    van Vlerken LE, Amiji MM (2006) Multi-functional polymeric nanoparticles for tumour-targeted drug delivery. Expert Opin Drug Deliv 3(2):205–216PubMedCrossRefGoogle Scholar
  17. 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 8:33Google Scholar
  18. 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):3724–3730PubMedCrossRefGoogle Scholar
  19. 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):1590–1598PubMedCrossRefGoogle Scholar
  20. 20.
    Liaudet L, Soriano FG, Szabo C (2000) Biology of nitric oxide signaling. Crit Care Med 28(4 Suppl):N37–N52PubMedCrossRefGoogle Scholar
  21. 21.
    Jang SH, Wientjes MG, Lu D, Au JL (2003) Drug delivery and transport to solid tumors. Pharm Res 20(9):1337–1350PubMedCrossRefGoogle Scholar
  22. 22.
    Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407(6801):249PubMedCrossRefGoogle Scholar
  23. 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):1310–1316CrossRefGoogle Scholar
  24. 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)Google Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2012

Authors and Affiliations

  • Alka Madaan
    • 1
  • Pratibha Singh
    • 1
  • Anshumali Awasthi
    • 1
  • Ritu Verma
    • 1
  • Anu T. Singh
    • 1
  • Manu Jaggi
    • 1
  • Shiva Kant Mishra
    • 3
  • Sadanand Kulkarni
    • 3
  • Hrishikesh Kulkarni
    • 2
  1. 1.Dabur Research FoundationsGhaziabadIndia
  2. 2.Fresenius Kabi Asia Pacific LimitedWanchaiHong Kong
  3. 3.Medical Affairs and Clinical ResearchFresenius Kabi India Private LimitedGurgaonIndia

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