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In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages

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Abstract

Purpose

Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages.

Methods

Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques.

Results

The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary.

Conclusion

Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

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Abbreviations

Abs:

Absorbance

DD:

Deacetylation degree

DSC:

Differential scanning calorimetry

EDTA:

Ethylene diamine tetraacetate

FTIR:

Fourier transform infrared spectrometry

HCS:

High molecular weight chitosan

HIV:

Human immunodeficiency virus

KBr:

Potassium bromide

LCS:

Low molecular weight chitosan

MCS:

Medium molecular weight chitosan

MTT:

(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

OCS:

Oligochitosan

TIRF:

Total internal reflection fluorescence

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors wish to express their heart-felt gratitude to Universiti Teknologi MARA for fund (0141903) and facility support.

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Authors and Affiliations

  1. Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia

    Siti Haziyah Mohd Chachuli, Asif Nawaz, Kifayatullah Shah, Idanawati Naharudin & Tin Wui Wong

  2. Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia

    Siti Haziyah Mohd Chachuli, Asif Nawaz, Kifayatullah Shah, Idanawati Naharudin & Tin Wui Wong

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  1. Siti Haziyah Mohd Chachuli
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  2. Asif Nawaz
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Correspondence to Tin Wui Wong.

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Chachuli, S.H.M., Nawaz, A., Shah, K. et al. In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages. Pharm Res 33, 1497–1508 (2016). https://doi.org/10.1007/s11095-016-1893-5

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  • DOI: https://doi.org/10.1007/s11095-016-1893-5

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