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Apoptosis induction and anti-cancer activity of LeciPlex formulations

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Abstract

Purpose

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery.

Methods

Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential.

Results

In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system.

Conclusions

Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

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Abbreviations

LP:

LeciPlex

CTAB:

Cetyltrimethylammonium bromide

DDAB:

Didodecyldimethylammonium bromide

HNSSC:

Head and Neck Squamous Cell Carcinoma

FBM:

Fetal Buccal Mucosa

PL:

90G Phospholipon 90G

CTAB-LeciPlex:

(CTLP)

DDLP:

DDAB-LeciPlex

PI:

Polydispersity

QR:

Quercetin.

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Acknowledgments

The authors are thankful to Lipoid GmBH, Germany, for providing samples of various phospholipids as gifts. The authors would also like to thank Gattefosse India Ltd., Mumbai, India, Gangwal Chemicals, Mumbai, India for providing samples of Transcutol HP and trehalose as gifts, respectively. The authors wish to thank Mr. D.D. Bhogale and Prof. D.C. Kothari of the Centre for Nanosciences and Nanotechnology, University of Mumbai, for the fluorescence measurements. The authors also wish to thank the All India Council for Technical Education (AICTE) and the Amrut Mody Research Fund (AMRF) for providing financial assistance. In addition, the authors wish to thank Dr. Krishna Iyer, Prof. at Bombay College of Pharmacy, for his help in preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department Of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz, Mumbai, Maharashtra, 400098, India

    Vivek V. Dhawan, Ankitkumar S. Jain & Mangal S. Nagarsenker

  2. Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, Maharashtra, 410210, India

    Ganesh V. Joshi, Yuvraj P. Nikam, Rajiv P. Gude & Rita Mulherkar

Authors
  1. Vivek V. Dhawan
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  2. Ganesh V. Joshi
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Correspondence to Mangal S. Nagarsenker.

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Dhawan, V.V., Joshi, G.V., Jain, A.S. et al. Apoptosis induction and anti-cancer activity of LeciPlex formulations. Cell Oncol. 37, 339–351 (2014). https://doi.org/10.1007/s13402-014-0183-7

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  • DOI: https://doi.org/10.1007/s13402-014-0183-7

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