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Liposome size and charge optimization for intraarterial delivery to gliomas

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Abstract

Nanoparticles such as liposomes may be used as drug delivery vehicles for brain tumor therapy. Particle geometry and electrostatic properties have been hypothesized to be important determinants of effective tumor targeting after intraarterial injection. In this study, we investigate the combined roles of liposome size and surface charge on the effectiveness of delivery to gliomas after intraarterial injection. Intracarotid injection of liposomes was performed in separate cohorts of both healthy and C6 glioma-bearing Sprague Dawley rats after induction of transient cerebral hypoperfusion. Large (200 nm) and small (60–80 nm) fluorescent dye-loaded liposomes that were either cationic or neutral in surface charge were utilized. Delivery effectiveness was quantitatively measured both with real-time, in vivo and postmortem diffuse reflectance spectroscopy. Semi-quantitative multispectral fluorescence imaging was also utilized to assess the pattern and extent of liposome targeting within tumors. Large cationic liposomes demonstrated the most effective hemispheric and glioma targeting of all the liposomes tested. Selective large cationic liposome retention at the site of glioma growth was observed. The liposome deposition pattern within tumors after intraarterial injection was variable with both core penetration and peripheral deposition observed in specific tumors. This study provides evidence that liposome size and charge are important determinants of effective brain and glioma targeting after intraarterial injection. Our results support the future development of 200-nm cationic liposomal formulations of candidate intraarterial anti-glioma agents for further pre-clinical testing.

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Authors and Affiliations

  1. Department of Anesthesiology, Columbia University Medical Center, 630 West 168th Street, P&S Box 46, New York, NY, 10032, USA

    Shailendra Joshi, Johann R. N. Cooke & Mei Wang

  2. Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA

    Darren K. W. Chan & Robert M. Straubinger

  3. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Jason A. Ellis & Jeffrey N. Bruce

  4. Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA

    Shaolie S. Hossain

  5. Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX, USA

    Shaolie S. Hossain

  6. Department of Electrical Engineering, Columbia University, New York, NY, USA

    Rajinder P. Singh-Moon

  7. Department of Electrical Engineering and Biomedical Engineering, Boston University, Boston, MA, USA

    Irving J. Bigio

  8. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA

    Robert M. Straubinger

Authors
  1. Shailendra Joshi
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  2. Johann R. N. Cooke
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  6. Rajinder P. Singh-Moon
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  7. Mei Wang
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Correspondence to Shailendra Joshi.

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Ethical standards

All the experiments reported comply with the current laws of the USA. All the experiments were approved by the Columbia University Institutional Review Board and the Animal Care and Use Committee.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This study was funded by the National Cancer Institute at the National Institutes of Health RO1-CA-138643.

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Joshi, S., Cooke, J.R.N., Chan, D.K.W. et al. Liposome size and charge optimization for intraarterial delivery to gliomas. Drug Deliv. and Transl. Res. 6, 225–233 (2016). https://doi.org/10.1007/s13346-016-0294-y

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  • DOI: https://doi.org/10.1007/s13346-016-0294-y

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