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

Abstract

Hydrogels warrant attention as a potential material for use in sustained pulmonary drug delivery due to their swelling and mucoadhesive features. Herein, hyaluronic acid (HA) is considered a promising material due to its therapeutic potential, the effect on lung inflammation, and possible utility as an excipient or drug carrier. In this study, the feasibility of using HA hydrogels (without a model drug) to engineer inhalation powders for controlled pulmonary drug delivery was assessed. A combination of chemical crosslinking and spray-drying was proposed as a novel methodology for the preparation of inhalation powders. Different crosslinkers (urea; UR and glutaraldehyde; GA) were exploited in the hydrogel formulation and the obtained powders were subjected to extensive characterization. Compositional analysis of the powders indicated a crosslinked structure of the hydrogels with sufficient thermal stability to withstand spray drying. The obtained microparticles presented a spherical shape with mean diameter particle sizes from 2.3 ± 1.1 to 3.2 ± 2.9 μm. Microparticles formed from HA crosslinked with GA exhibited a reasonable aerosolization performance (fine particle fraction estimated as 28 ± 2%), whereas lower values were obtained for the UR-based formulation. Likewise, swelling and stability in water were larger for GA than for UR, for which the results were very similar to those obtained for native (not crosslinked) HA. In conclusion, microparticles could successfully be produced from crosslinked HA, and the ones crosslinked by GA exhibited superior performance in terms of aerosolization and swelling.

In Vitro and Ex Vivo Investigation of the Effects of Polydopamine Nanoparticle Size on Their Antioxidant and Photothermal Properties: Implications for Biomedical Applications

“…Larger nanoparticles are instead preferable for photothermal therapy treatments: indeed, as evidenced by our tests on U-87 cells, PDNPs of 957 nm in diameter can raise the intracellular temperature over 42°C, suitable for hyperthermia . Owing to the improved photothermal transduction efficiency, PDNPs with diameter > 900 nm can be also considered for controlled drug release applications; however, the relatively big size of these particles may limit their exploitation for brain delivery applications due to the expected low blood–brain barrier (BBB) crossing efficiency. In conclusion, all of the collected data provide useful knowledge to tailor the most appropriate PDNP size according to the intended biomedical application.…”

A physicochemical double-cross-linked gelatin hydrogel with enhanced antibacterial and anti-inflammatory capabilities for improving wound healing

“…It is considered to be the most effective wound healing material [5][6][7]. To date, a wide variety of hydrogel dressings have been prepared using synthetic or natural polymers as raw materials, by means of chemical, physical, and enzymatic cross-linking [8][9][10]. However, in the preparation of hydrogels, the complex chemical modification of matrix materials and the use of special chemical cross-linking agents may greatly limit the commercial production and application of hydrogels [11,12].…”

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders

“…HA can be modified with thiols, haloacetates, dihydrazides, aldehydes, or carbodiimide moieties to facilitate cross-linking into a gel [ 87 ]. HA-based hydrogels have been used in various biomedical applications including controlled drug delivery [ 98 ]. A recent study assessed the feasibility of HA hydrogels as carriers for controlled pulmonary drug delivery of inhalation powders and their finding showed that HA hydrogels could successfully be used as drug carriers for sustained pulmonary delivery [ 98 ].…”