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Dual drug delivery using “smart” liposomes for triggered release of anticancer agents

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Abstract

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel–topotecan (Pac–Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000–DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000–DSPE:DSPE–PEG–folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac–Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called “smart liposomes” which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

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Acknowledgments

We wish to acknowledge Dr. Dhiraj Khattar (Director, Formulation Development & Delivery Systems), Fresenius Kabi Oncology Ltd., Haryana (India) for rendering gift samples of Pac and Top. We would also like to thank University Grant Commission (UGC), Delhi for financial support as Junior Research Fellowship (JRF) to one of the authors namely Ankit Jain for carrying out this work. We are obliged to Mr. Prakash Arora, GE Healthcare (India) for providing Hi-Trap® columns as gift samples. We also acknowledge AIIMS, Delhi for Transmission Electron Microscopy.

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Authors and Affiliations

  1. Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, 470 003, Madhya Pradesh, India

    Ankit Jain, Arvind Gulbake, Ashish Jain, Satish Shilpi, Pooja Hurkat & Sanjay K. Jain

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  1. Ankit Jain
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  2. Arvind Gulbake
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  3. Ashish Jain
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  4. Satish Shilpi
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  5. Pooja Hurkat
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  6. Sanjay K. Jain
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Correspondence to Sanjay K. Jain.

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Jain, A., Gulbake, A., Jain, A. et al. Dual drug delivery using “smart” liposomes for triggered release of anticancer agents. J Nanopart Res 15, 1772 (2013). https://doi.org/10.1007/s11051-013-1772-5

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