Nanoforming Hyaluronan-Based Thermoresponsive Hydrogels: Optimized and Tunable Functionality in Osteoarthritis Management

Hyaluronic acid (HA) constitutes a versatile chemical framework for the development of osteoarthritis pain treatment by means of injection in the joints, so-called viscosupplementation. Without appropriate physico-chemical tuning, such preparations are inherently hindered by prompt in vivo degradati...

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Bibliographic Details
Published in:Pharmaceutics 2022-03, Vol.14 (3), p.659
Main Authors: Porcello, Alexandre, Gonzalez-Fernandez, Paula, Jordan, Olivier, Allémann, Eric
Format: Article
Language:English
Subjects:
Arthritis
biodegradation
hyaluronic acid
Lubricants & lubrication
Molecular weight
Morphology
Nanoparticles
Osteoarthritis
Oxidative stress
Physiology
Polymers
Rheology
Scanning electron microscopy
Scientific imaging
thermoresponsiveness
Viscoelasticity
viscosupplementation
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Summary:Hyaluronic acid (HA) constitutes a versatile chemical framework for the development of osteoarthritis pain treatment by means of injection in the joints, so-called viscosupplementation. Without appropriate physico-chemical tuning, such preparations are inherently hindered by prompt in vivo degradation, mediated by hyaluronidases and oxidative stress. To prolong hydrogel residence time and confer optimized product functionality, novel thermoresponsive nanoforming HA derivatives were proposed and characterized. Combined use of sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly( -isopropylacrylamide) in green chemistry process enabled the synthesis of HA-based polymers, with in situ obtention of appropriate viscoelastic properties. Spontaneous and reversible thermoformation of nanoparticles above 30 °C was experimentally confirmed. Lead formulations were compared to a commercially available HA-based product and shown significantly better in vitro resistance to enzymatic and oxidative degradation, required half the injection force with optimal viscoelastic hydrogel properties in equine synovial fluids. Results highlighted the vast potential of appropriately engineered HA-based systems as next-generation long-acting viscosupplementation products for osteoarthritic patients.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14030659