Siti Haziyah Mohd Chachuli1,2, Asif Nawaz1,2, Kifayatullah Shah1,2, Idanawati Naharudin1,2, Tin Wui Wong3,4. 1. Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia. 2. Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia. 3. Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia. wongtinwui@salam.uitm.edu.my. 4. Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, 42300, Selangor, Malaysia. wongtinwui@salam.uitm.edu.my.
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.
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.
Authors: Ruhisy Mohd Rasul; M Tamilarasi Muniandy; Zabliza Zakaria; Kifayatullah Shah; Chin Fei Chee; Ali Dabbagh; Noorsaadah Abd Rahman; Tin Wui Wong Journal: Carbohydr Polym Date: 2020-08-18 Impact factor: 9.381