Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery-A Particle Engineering Approach

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Drug Delivery

Background:

• Hydrogels offer potential for sustained pulmonary drug delivery due to swelling and mucoadhesive properties.
• Hyaluronic acid (HA) is a promising biomaterial with therapeutic benefits and potential as an excipient or drug carrier for lung applications.

Purpose of the Study:

• To assess the feasibility of using HA hydrogels to engineer inhalation powders for controlled pulmonary drug delivery.
• To develop and characterize HA-based microparticles for inhalation using chemical crosslinking and spray-drying.

Main Methods:

• Hyaluronic acid hydrogels were formulated with urea (UR) or glutaraldehyde (GA) as crosslinkers.
• Hydrogels were processed into microparticles via spray-drying.
• Characterization included compositional analysis, thermal stability, particle size, shape, aerosolization performance, swelling, and stability in water.

Main Results:

• Spray-dried HA microparticles exhibited spherical morphology with sizes ranging from 2.3 to 3.2 μm.
• Glutaraldehyde-crosslinked HA microparticles demonstrated superior aerosolization performance (28 ± 2% fine particle fraction) compared to urea-crosslinked ones.
• GA-crosslinked HA showed enhanced swelling and stability in water relative to UR-crosslinked HA and native HA.

Conclusions:

• Microparticles for controlled pulmonary drug delivery can be successfully produced from crosslinked hyaluronic acid.
• Glutaraldehyde crosslinking of HA yields microparticles with improved aerosolization and swelling properties, making them suitable for pulmonary applications.