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In vitro mechanistic study of cell death and in vivo performance evaluation of RGD grafted PEGylated docetaxel liposomes in breast cancer

  • Sachin Naik, MPharm

      Affiliations

    • Pharmacy Department, NDDS Laboratory, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India
    • ,
  • Deepa Patel, MPharm

      Affiliations

    • Pharmacy Department, NDDS Laboratory, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India
    • ,
  • Krishna Chuttani, PhD

      Affiliations

    • Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, India
    • ,
  • Anil K. Mishra, PhD

      Affiliations

    • Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, India
    • ,
  • Ambikanandan Misra, PhD

      Affiliations

    • Pharmacy Department, NDDS Laboratory, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Gujarat, India
    • Corresponding Author InformationCorresponding author: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Post Box No. 51, Kalabhavan, Vadodara - 390 001, Gujarat state, India.

Received 6 July 2011; accepted 9 November 2011. published online 23 November 2011.
Corrected Proof

Abstract 

Objectives of the investigations were to prepare RGD grafted docetaxel liposomes (RGD-PEG-LP-DC) using supercritical fluid technology and evaluate it in vitro for cytotoxicity, DNA content analysis, mechanism of cell death, and in vivo for pharmacokinetic and biodistribution studies in BALB/c mice. The RGD-PEG-LP-DCs were found to be most cytotoxic in BT-20 and MDA-MB-231 cell lines. The flowcytometry results shows at 48 hours, 96% G2 phase arrest for RGD-PEG-LP-DC at 5 nM drug concentration. The mode of cell death was found to be mainly by necrosis at low drug equivalent concentration (1 nM) and by apoptosis at high drug equivalent concentration (10 nM). With increase in time and concentration the mode of cell death by apoptosis was found to be increasing. Biodistribution demonstrated that site specific drug distribution, t1/2, and MRT improved significantly for RGD-PEG-LP-DC. From the studies site specific and sustained intracellular drug delivery from RGD-PEG-LP-DCs may provide promising strategy in enhancing embattled against breast cancer treatment.

Graphical Abstract 

Key words: RGD, Supercritical fluid technology, BT-20, MDA-MB-231, Ehrlich ascites tumor

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 Authors disclose there is not any commercial association for the research work presented in current article.

 The study received support from University Grant Commission and Technology Information Forecasting Assessment Council (TIFAC), Department of Science and Technology, Government of India.

PII: S1549-9634(11)00529-6

doi:10.1016/j.nano.2011.11.008

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