Dispersible hydrolytically sensitive nanoparticles for nasal delivery of thyrotropin releasing hormone (TRH)

Moran Haim Zada, Michael Kubek, Wahid Khan, Awanish Kumar, Abraham Domb

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Nose-to-brain delivery of drugs is affected by nanoparticles (NPs) deposited on the olfactory surface and absorbed directly into the brain. Thyrotropin releasing hormone (TRH), a water soluble drug used for treating suicidal patients, was incorporated into a fast degrading poly(sebacic anhydride) (PSA) NPs. NPs were prepared by a solvent-antisolvent process under strict anhydrous environment to obtain high TRH loading and to avoid premature PSA degradation and TRH release. PSA and TRH were dissolved in a mixture of dichloromethane and ethanol and added dropwise to a dispersion of mannitol particles in heptane as an antisolvent. Mannitol powder was included in the antisolvent, so that formed NPs adhered to the mannitol microparticles for easy isolation and immediate dispersion in water prior to use. The size, surface charge, and morphology of the TRH-PSA NPs were determined using dynamic light scattering (DLS), zeta-potential, and Scanning Electron Microscopy (SEM), respectively. The NPs prepared were uniform and spherical of ~250 nm. Further, the in vitro release profile of TRH from NPs lasted for 12 h with most TRH released within the first hour in water. Concentration dependent cell toxicity studies revealed low toxicity level at low concentrations of the NPs. Surface adsorption of the NPs was also uniform on the cell surface as examined through the odyssey near infrared fluorescence (NIR) images using Indocyanine green (ICG). The NPs are designed to enable direct delivery to the olfactory epithelium using a refillable nasal atomizer that deposits mist onto the olfactory neuro-epithelium.

Original languageEnglish
Pages (from-to)278-289
Number of pages12
JournalJournal of Controlled Release
Volume295
DOIs
StatePublished - 10 Feb 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Funding

We thank Gadi Cohen (PhD), student of Prof. Philip Lazarovici, Faculty of Medicine, Institute for Drug Research, The Hebrew University of Jerusalem, for the cell line experiments.

FundersFunder number
Hebrew University of Jerusalem
Faculty of Medicine, Prince of Songkla University

    Keywords

    • Nanoparticles
    • Nasal delivery
    • Poly(sebacic anhydride) (PSA)
    • Thyrotropin releasing hormone (TRH)

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