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Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols
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Enhanced nasal drug delivery efficiency by increasing mechanical loading using hypergravity.

Dongjoo Kim1,2, Young Hyo Kim1,3, Soonjo Kwon4,5

  • 1WCSL of Integrated Human Airway-on-a-chip, Inha University, Incheon, 22212, Korea.

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Summary
This summary is machine-generated.

Hypergravity exposure enhances nasal drug delivery by temporarily weakening the nasal mucosa barrier. This novel method improves the absorption of polar molecules, offering a new strategy for drug administration.

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Area of Science:

  • Pharmacology and Drug Delivery
  • Biophysics and Cell Biology

Background:

  • Nasal drug administration is attractive due to high vascularization and surface area.
  • Nasal mucosa has limited permeability to polar molecules, hindering drug absorption.
  • Novel strategies are needed to enhance nasal drug delivery efficiency.

Purpose of the Study:

  • To investigate hypergravity as a novel method for improving polar drug absorption via the nasal route.
  • To assess the impact of hypergravity on nasal epithelial cell permeability and barrier function.

Main Methods:

  • Exposure of RPMI 2650 and primary human nasal epithelial cells to hypergravity (10 × g) for 20-minute intervals.
  • Measurement of transepithelial electrical resistance (TEER) to assess barrier integrity.
  • Quantification of cellular permeability using fluorescein sodium salt (NaFI) and FITC-labeled dextran (FD-4).
  • Analysis of cytoskeletal structures and tight junctions using immunostaining and RT-qPCR.

Main Results:

  • Hypergravity exposure decreased TEER, indicating a weakened cell barrier.
  • Cellular permeability increased by 19% for NaFI and 16% for FD-4.
  • Hypergravity affected cytoskeletal structures and tight junctions, compromising barrier function without significant loss of metabolic activity.

Conclusions:

  • Hypergravity can transiently increase nasal epithelial permeability to polar molecules.
  • This approach offers a promising new strategy for enhancing nasal drug absorption.
  • Further research can explore the therapeutic potential of hypergravity in drug delivery.