Pharmaceutical Chemistry Journal

, Volume 51, Issue 11, pp 1005–1013 | Cite as

Synthesis, Characterization, Pharmacokinetics and Evaluation of Cytotoxicity for Docetaxel-Oleate Conjugate Targeting MCF-7 Breast Cancer Cells

  • Neela M. Bhatia
  • Pragati K. Kulkarni
  • Snehal S. Ashtekar
  • Deepak V. Mahuli
  • Manish S. Bhatia

The present work envisages synthesis of an ester conjugate of anticancer drug docetaxel with oleoyl chloride, with the aim to selectively target the breast cancer cells MCF-7 so as to minimize non-specific hemolytic side effects. The synthesized docetaxel-oleate conjugate was characterized and confirmed by physicochemical and spectral methods. Solubility and partition coefficient determination indicated increased solubility and lipophilicity, while protein binding studies revealed low protein binding capacity of the conjugated drug. Subsequently, the conjugate was evaluated for its in vitro cytotoxicity, drug release, and hemolysis effects. The results indicated a lesser RBC lysis at a more significant anticancer activity of the parent drug and a selective diffusion at pH of cancer cells (compared to the pH of normal cells), thereby increasing specificity and decreasing adverse effects. In addition, an analytical HPLC method was developed for hydrolytic study of the conjugated drug. The proposed method showed good separation of the target compounds with high accuracy and precision. Hydrolysis study indicated a minimum hydrolysis of the conjugate at various pH that simulated gastric and intestinal fluids. Thus, the synthesized conjugate proves to be a useful prodrug in reducing systemic toxicity of docetaxel as well as selectively targeting cancerous cells.


Synthesis docetaxel-oleate conjugate prodrug targeted drug delivery breast cancer 



The authors are thankful to Dr. H. N. More – Principal, Bharati Vidyapeeth College of Pharmacy, Kolhapur for providing laboratory facilities.

Conflict of Interest

The authors declare that they have no conflict of interest for the submitted work.


  1. 1.
    K. H. Bae, H. J. Chung and T. G. Park, Mol. Cells, 31, 295 – 302 (2011).CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    A. Varanasi, G. P. L. Jaya Sree, R. Yamaganti, et al., Int. J. Sci. Eng. Res., 6, 833 – 840 (2015).Google Scholar
  3. 3.
    G. Gellerman, S. Baskin, L. Galia, et al., Anti-Cancer Drugs, 24, 112 – 119 (2013).CrossRefPubMedGoogle Scholar
  4. 4.
    F. Kratz, J. Control. Release, 32, 171 – 183 (2008).CrossRefGoogle Scholar
  5. 5.
    M. C. Garnett, Adv. Drug Deliv. Rev., 53, 171 – 216 (2001).CrossRefPubMedGoogle Scholar
  6. 6.
    H. Han and G. Amidon, AAPS Pharm. Sci., 2, 48 – 58 (2000).CrossRefGoogle Scholar
  7. 7.
    S. Mitra, U. Gaur, P. C. Ghosh, and A. N. Maitra, J. Control. Release, 4, 317 – 23 (2001).CrossRefGoogle Scholar
  8. 8.
    I. Youm and V. Agrahari, Cancer Cell Microenviron., 2, e689 (2015)Google Scholar
  9. 9.
    D. T. Win, Assumption Univ. J. Technol., 9, 75 – 78 (2005).Google Scholar
  10. 10.
    C. Carrillo, M. D. M. Cavia, and S. R. Alonso-Torre, Nutr. Hosp., 27, 1860 – 1865 (2012).PubMedGoogle Scholar
  11. 11.
    A. Furniss, A. Hannaford, and P. Smith, Vogel’s Textbook of Practical Organic Chemistry, ELBS Publications, New York (1988), pp. 692 – 693.Google Scholar
  12. 12.
    N. Bhatia, K. Katkar, and S. Ashtekar, Asian J. Pharm. Sci., 11, 449 – 458 (2016).CrossRefGoogle Scholar
  13. 13.
    A. Rasheed and C. K. Ashok Kumar, Int. J. Curr. Pharm. Res., 1, 47 – 55 (2009).Google Scholar
  14. 14.
    S. B. Bhise, R. J. Dias, S. G. Dhavale, and K. K. Mali, Laboratory Manual of Biopharmaceutics and Pharmakokinetics, Trinity Publishing House, India (2010), pp. 1 – 66.Google Scholar
  15. 15.
    V. K. Singh and B. B. Subudhi, Med. Chem. Res., DOI (2014).
  16. 16.
    K. K. Upadhyay, A. N. Bhatt, E. Castro, et al., Macromol. Biosci., 10, 503 – 512 (2010).CrossRefPubMedGoogle Scholar
  17. 17.
    M. K. Lee, S. J. Lim, and C. K. Kim, Biomaterials, 28, 2137 – 4216 (2007).CrossRefPubMedGoogle Scholar
  18. 18.
    X. Zhao, X. Tao, D. Wei, Q. Song, Eur. J. Med. Chem., 41, 1352 – 1358 (2006).CrossRefPubMedGoogle Scholar
  19. 19.
    M. Trebunova, G. Laputkova, E. Slaba, et al., Anticancer Res., 32, 2849 – 2854 (2012).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Neela M. Bhatia
    • 1
  • Pragati K. Kulkarni
    • 1
  • Snehal S. Ashtekar
    • 1
  • Deepak V. Mahuli
    • 2
  • Manish S. Bhatia
    • 3
  1. 1.Department of Quality AssuranceBharati Vidyapeeth College of PharmacyKolhapurIndia
  2. 2.Department of PharmacologyBharati Vidyapeeth College of PharmacyKolhapurIndia
  3. 3.Department of Pharmaceutical ChemistryBharati Vidyapeeth College of PharmacyKolhapurIndia

Personalised recommendations