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Assaying Mucus Adhesion of Oral Drug Delivery Carriers On Gut-on-A-Chip Model

Khodabandehloo, Amir Hossein | 2024

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 57239 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Taghipoor, Mojtaba; Mashayekhan, Shohreh
  7. Abstract:
  8. This study aimed to investigate the penetration of Niosome drug nanocarriers containing curcumin and the effect of PEG surface modification on them in the mucus using a microfluidic chip. The main mucus-forming substance, mucin-type 2, was obtained by extracting from the small intestine of sheep and using calcium ion that regulates the gel properties of the mucus; three different groups, with calcium concentrations of 5, 10, and 15 mM of Calcium were studied as a representative of healthy and Diseased person's mucus. In this research, the study was done on a microfluidic chip; In the processes associated with fabrication of the chip, photolithography, soft lithography, and laser cutting methods were utilized. Also, the final mold was sandwich-like, and the main PDMS chip was bonded on one side of 3 mm thick plexiglass plates with a 5% APTES solution. Also, in order to seal the chip, two plexiglass plates were aligned and then tied using a clamp by pouring pure acetic acid (as a photoinitiator) and curing with UV light for 5 minutes, leading to a leakless integrated device. The main PDMS chip was designed membrane-free, which owns a three-channel geometry, and was inspired by the anatomy of the human small intestine, and the channels represented the inner lumen of the intestine where the drug enters, the stabilized mucus gel, and the third one channel, which was innovative compared to previous related research, played the role of a capillary for drug collection. Finally, thanks to the fluorescent property of curcumin drug, imaging was done by fluorescent microscopy, and using ImageJ image analysis software, these qualitative images were quantified to determine parameters such as effective diffusion coefficient, and the effect of pegylation on mucopentration of the modified surface of niosomes and pristine niosomes. To conclude, based on the results, PEG-modified niosomes showed a higher penetration rate than unmodified niosomes thanks to the neutralization nature of the PEGylation on the surface of niosomes. The PEG-modified niosomes showed effective diffusion coefficient of 0.38 μm^2/s in compared to non-modified niosomes with effective diffusion coefficient of 0.21 μm^2/s in the defected mucus group
  9. Keywords:
  10. Curcumin ; Niosome ; Oral Drug Delivery ; Disease Modeling ; Gut-on-A-Chip ; Mucus ; Mucus-on-A-Chip

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