Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery

Shital Lungare, Keith Hallam, Raj K.S. Badhan

Research output: Contribution to journalArticle

Abstract

Central nervous system (CNS) drug delivery is often hampered due to the insidious nature of the blood-brain barrier (BBB). Nose-to-brain delivery via olfactory pathways have become a target of attention for drug delivery due to bypassing of the BBB. The antioxidant properties of phytochemicals make them promising as CNS active agents but possess poor water solubility and limited BBB penetration. The primary aim of this study was the development of mesoporous silica nanoparticles (MSNs) loaded with the poorly water-soluble phytochemicals curcumin and chrysin which could be utilised for nose-to-brain delivery. We formulated spherical MSNP using a templating approach resulting in ∼220nm particles with a high surface porosity. Curcumin and chrysin were successfully loaded into MSNP and confirmed through Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC approaches with a loading of 11-14% for curcumin and chrysin. Release was pH dependant with curcumin demonstrating increased chemical stability at a lower pH (5.5) with a release of 53.2%±2.2% over 24h and 9.4±0.6% for chrysin. MSNP were demonstrated to be non-toxic to olfactory neuroblastoma cells OBGF400, with chrysin (100μM) demonstrating a decrease in cell viability to 58.2±8.5% and curcumin an IC50 of 33±0.18μM. Furthermore confocal microscopy demonstrated nanoparticles of <500nm were able to accumulate within cells with FITC-loaded MSNP showing membrane localised and cytoplasmic accumulation following a 2h incubation. MSNP are useful carriers for poorly soluble phytochemicals and provide a novel vehicle to target and deliver drugs into the CNS and bypass the BBB through olfactory drug delivery.

LanguageEnglish
Pages280-293
Number of pages14
JournalInternational Journal of Pharmaceutics
Volume513
Issue number1-2
Early online date12 Sep 2016
DOIs
Publication statusPublished - 20 Nov 2016

Fingerprint

Curcumin
Phytochemicals
Nose
Silicon Dioxide
Nanoparticles
Central Nervous System Agents
Blood-Brain Barrier
Brain
Pharmaceutical Preparations
Olfactory Esthesioneuroblastoma
Olfactory Pathways
Water
Fluorescein-5-isothiocyanate
Porosity
Differential Scanning Calorimetry
Confocal Microscopy
Solubility
Inhibitory Concentration 50
Spectrum Analysis
Cell Survival

Bibliographical note

© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ijpharm.2016.09.042

Keywords

  • Flavonoid
  • Mesoporous silica nanoparticle
  • Nose-to-brain
  • Olfactory
  • Phytochemical

Cite this

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abstract = "Central nervous system (CNS) drug delivery is often hampered due to the insidious nature of the blood-brain barrier (BBB). Nose-to-brain delivery via olfactory pathways have become a target of attention for drug delivery due to bypassing of the BBB. The antioxidant properties of phytochemicals make them promising as CNS active agents but possess poor water solubility and limited BBB penetration. The primary aim of this study was the development of mesoporous silica nanoparticles (MSNs) loaded with the poorly water-soluble phytochemicals curcumin and chrysin which could be utilised for nose-to-brain delivery. We formulated spherical MSNP using a templating approach resulting in ∼220nm particles with a high surface porosity. Curcumin and chrysin were successfully loaded into MSNP and confirmed through Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC approaches with a loading of 11-14{\%} for curcumin and chrysin. Release was pH dependant with curcumin demonstrating increased chemical stability at a lower pH (5.5) with a release of 53.2{\%}±2.2{\%} over 24h and 9.4±0.6{\%} for chrysin. MSNP were demonstrated to be non-toxic to olfactory neuroblastoma cells OBGF400, with chrysin (100μM) demonstrating a decrease in cell viability to 58.2±8.5{\%} and curcumin an IC50 of 33±0.18μM. Furthermore confocal microscopy demonstrated nanoparticles of <500nm were able to accumulate within cells with FITC-loaded MSNP showing membrane localised and cytoplasmic accumulation following a 2h incubation. MSNP are useful carriers for poorly soluble phytochemicals and provide a novel vehicle to target and deliver drugs into the CNS and bypass the BBB through olfactory drug delivery.",
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Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery. / Lungare, Shital; Hallam, Keith; Badhan, Raj K.S.

In: International Journal of Pharmaceutics, Vol. 513, No. 1-2, 20.11.2016, p. 280-293.

Research output: Contribution to journalArticle

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AU - Lungare, Shital

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AU - Badhan, Raj K.S.

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