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Phospholipid Magnesome—a nasal vesicular carrier for delivery of drugs to brain

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Abstract

The goal of this work was to investigate a new nasal carrier for enhanced drug delivery to brain, we call Phospholipid Magnesome. The system contains soft phospholipid vesicles, composed of phospholipid, water, propylene glycol, magnesium salt, and the mucoadhesive polymer, alginate. The carrier was characterized by various methods: electron microscopy, calorimetry, and dynamic light scattering. The ability of the carrier’s vesicles to entrap various molecules was studied by CLSM and ultracentrifugation combined with HPLC quantification. Mucoadhesivity of the carrier was tested in vitro using porcine nasal mucosa. The delivery of rohdamine 6G, insulin, and epidermal growth factor was estimated by two methods, multiphoton microscopy and near infrared (NIR) imaging. Pharmacodynamic effects of nasal treatment with oxytocin and insulin incorporated in Phospholipid Magnesome were evaluated in animal models. Results show that the system is composed of soft multilamellar nanosized vesicles with the ability to entrap both lipophilic and hydrophilic molecules. The mucoadhesivity test results indicate a prolonged contact time of the drug with the nasal membrane as compared to control. Multiphoton microscopy and NIR imaging of brain show effective delivery of the tested molecules to brain following nasal administration in Phospholipid Magnesome relative to controls. Moreover, the results of the pharmacodynamic study measuring the antinociceptive effect of oxytocin administrated nasally to an animal model indicate the efficiency of the Phospholipid Magnesome as compared to three control systems. Further, nasal administration of insulin resulted in a strong and prolonged hypoglycemic effect for the drug incorporated in the new carrier but not for control systems. Based on the results of the histopathological test, the carrier is safe for local administration on the nasal membrane. In conclusion, the results of this study suggest that Phospholipid Magnesome nasal carrier is able to improve drug effects, probably by a combined mechanism, absorption enhancement, and prolongation of mucosal contact.

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Acknowledgements

The authors wish to thank Mrs. Shatha Boukaileh from Prof. Elka Touitou’s lab for help and assistance in the animal experiments, and Dr. Zakharia Manevitch from The Core of Research Facility, Faculty of Medicine, Hebrew University of Jerusalem for help in the Multiphoton microscopic experiments.

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Authors and Affiliations

  1. The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, PO Box 12065, 91120, Jerusalem, Israel

    Hiba Natsheh & Elka Touitou

Authors
  1. Hiba Natsheh
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  2. Elka Touitou
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Correspondence to Elka Touitou.

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All procedures performed on animals were according to The National Institute of Health regulations and were approved by the Committee for Animal Care and Experimental Use of the Hebrew University of Jerusalem.

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The authors declare that they have no competing interests.

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Natsheh, H., Touitou, E. Phospholipid Magnesome—a nasal vesicular carrier for delivery of drugs to brain. Drug Deliv. and Transl. Res. 8, 806–819 (2018). https://doi.org/10.1007/s13346-018-0503-y

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