Ionic-Liquid-Modified Nanoparticles as Potential Mucus Modulators for Nasal Drug Delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Mucosal barriers present significant challenges for effective drug delivery.
• Polymer nanoparticles (NPs) show promise for drug delivery but face diffusion limitations.
• Ionic liquids (ILs) offer tunable properties and biocompatibility for modulating biological barriers.

Purpose of the Study:

• To investigate the effect of choline carboxylic acid-based ILs on the diffusion of PLGA, PEG-PLGA, and PEG-PLA NPs through nasal mucus.
• To analyze the interactions between IL-modified NPs and mucin using spectroscopic and calorimetric techniques.
• To evaluate the potential of ILs for enhancing intranasal drug delivery using an ex vivo model.

Main Methods:

• Multiple particle tracking to measure NP diffusion rates in aqueous and mucosal environments.
• UV-vis spectroscopy and Circular Dichroism (CD) spectroscopy to study NP-mucin interactions and mucin structural changes.
• Isothermal titration calorimetry (ITC) for quantitative binding energy measurements.
• Ex vivo porcine nasal mucosa model for assessing intranasal delivery potential.

Main Results:

• Choline-based ILs altered NP diffusion rates, with specific ILs affecting different NP types differently (e.g., slowing PEG-PLGA, increasing PEG-PLA diffusion).
• ILs were shown to stabilize interactions between polymer NPs and mucin polymers.
• Spectroscopic and calorimetric data confirmed complex formation and binding energies between NPs and mucus.
• Ex vivo studies suggested a link between zwitterionic transport materials and improved nasal drug delivery.

Conclusions:

• Choline carboxylic acid-based ILs can modulate the transport behavior of polymer NPs in mucosal environments.
• These ILs demonstrate potential for controlling NP-mucin interactions, offering a strategy for enhanced intranasal drug delivery.
• The findings highlight the utility of ILs in overcoming mucosal barriers for improved therapeutic applications.