Pharmaceutical Research

, Volume 29, Issue 10, pp 2874–2886 | Cite as

Phosphatidylinositol 3-kinase Inhibitor (PIK75) Containing Surface Functionalized Nanoemulsion for Enhanced Drug Delivery, Cytotoxicity and Pro-apoptotic Activity in Ovarian Cancer Cells

  • Meghna Talekar
  • Srinivas Ganta
  • Amit Singh
  • Mansoor Amiji
  • Jackie Kendall
  • William A. Denny
  • Sanjay Garg
Research Paper



Ovarian cancer is a debilitating disease, which needs multi-pronged approach of targeted drug delivery and enhanced efficacy with the use of combination therapeutics. In this study, we have examined the anticancer activity of PIK75 incorporated in surface functionalized nanoemulsions for targeted delivery to SKOV-3 cells. A pro-apoptotic molecule C6-ceramide was also co-delivered to augment therapeutic efficacy.


EGFR and FR functionalized nanoemulsions incorporating PIK75 and C6-ceramide were characterized for particle size, surface charge, entrapment efficiency and morphology. Fluorescence and quantitative uptake studies were conducted in SKOV-3 cells to determine intracellular distribution. Cell viability was assessed using MTT assay while mechanism of cytotoxicity was evaluated using capsase-3/7, TUNEL and hROS assay.


Cytotoxicity assay showed 57% decrease in IC50 value of PIK75 following treatment with EGFR targeted nanoemulsion and 40% decrease following treatment with FR targeted nanoemulsion. Combination therapy with PIK75 and ceramide enhanced the cytotoxicity of PIK75 compared to therapy with individual formulations. The increase in cytotoxicity was attributed to increase in cellular apoptosis and hROS activity.


The results of this study showed that the targeted system improved cytotoxicity of PIK75 compared to the non-targeted system. Combination therapy with ceramide augmented PIK75’s therapeutic activity.


C6-ceramide EGFR folate nanoemulsion ovarian cancer. phosphatidylinositol 3-kinase inhibitor 





epidermal growth factor receptor


folate receptor




Phosphatidylinositol 3-kinase


Phosphatidylinositol 4, 5-diphosphate


Phosphatidylinositol 3, 4, 5-triphosphate


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Meghna Talekar
    • 1
  • Srinivas Ganta
    • 2
  • Amit Singh
    • 3
  • Mansoor Amiji
    • 3
  • Jackie Kendall
    • 4
  • William A. Denny
    • 4
  • Sanjay Garg
    • 1
    • 5
  1. 1.School of Pharmacy, Faculty of Medical & Health SciencesThe University of AucklandAucklandNew Zealand
  2. 2.Nemucore Medical Innovations, Inc.WorcesterUSA
  3. 3.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  4. 4.Auckland Cancer Society Research Centre Faculty of Medical & Health SciencesThe University of AucklandAucklandNew Zealand
  5. 5.School of Pharmacy & Medical SciencesUniversity of South Australia (UniSa)AdelaideAustralia

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