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Pharmaceutical Research

, Volume 31, Issue 9, pp 2490–2502 | Cite as

Development of EGFR-Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer

  • Srinivas Ganta
  • Amit Singh
  • Niravkumar R. Patel
  • Joseph Cacaccio
  • Yashesh H. Rawal
  • Barbara J. Davis
  • Mansoor M. Amiji
  • Timothy P. Coleman
Research Paper

ABSTRACT

Purpose

Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations.

Methods

The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP.

Results

The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®.

Conclusion

The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer.

KEY WORDS

C6-ceramide EGFR gadolinium MRI nanoemulsion ovarian cancer platinum 

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by the NIH grants (R43 CA144591 and U54 CA151881). Joseph Cacaccio and Yashesh Rawal received financial support from the Massachusetts Life Science Center Internship Challenge. Additionally, the authors thank Nanotechnology Characterization Lab (Fredrick, MD) for Pt analysis and Drs. Praveen Kulakarni and Craig Ferris in the Center for Translational Neuro-Imaging at Northeastern University (Boston, MA) for help with the MRI studies.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Srinivas Ganta
    • 1
  • Amit Singh
    • 2
  • Niravkumar R. Patel
    • 1
  • Joseph Cacaccio
    • 3
  • Yashesh H. Rawal
    • 3
  • Barbara J. Davis
    • 1
  • Mansoor M. Amiji
    • 2
    • 4
  • Timothy P. Coleman
    • 1
    • 3
    • 4
    • 5
  1. 1.Nemucore Medical Innovations, Inc.WorcesterUSA
  2. 2.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  3. 3.Blue Ocean Biomanufacturing, Inc.WorcesterUSA
  4. 4.Center for Translational Cancer Nanomedicine, Northeastern UniversityBostonUSA
  5. 5.Foundation for the Advancement of Personalized Medicine ManufacturingPhoenixUSA

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