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Home / Equine Research Bank / Pharmaceutics / Nanoforming Hyaluronan-Based Thermoresponsive Hydrogels: Opt...
Pharmaceutics2022; 14(3); doi: 10.3390/pharmaceutics14030659

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

Abstract: 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(N-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.
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Publication Date: 2022-03-17 PubMed ID: 35336034PubMed Central: PMC8955188DOI: 10.3390/pharmaceutics14030659Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research work involves the development of hyaluronic acid-based polymers that are thermally responsive to treat osteoarthritis pain. The new materials demonstrate increased resistance to in vivo degradation, lower injection force requirements, and improved viscoelastic properties, making them a promising next-generation solution for osteoarthritis management.

Introduction to Hyaluronic Acid and Osteoarthritis

  • The study presents hyaluronic acid (HA) as a core chemical structure used in treatments for osteoarthritis pain. These treatments often involve injecting HA into the joints, a process known as viscosupplementation. However, this treatment suffers from rapid degradation in the body due to the activity of enzymes called hyaluronidases and under conditions of oxidative stress.

Development of Thermoresponsive HA Derivatives

  • To overcome these shortcomings, the researchers propose and characterize new HA derivatives capable of forming nanoparticles in response to temperature change. These “nanoforming” derivatives can modify the physical and chemical characteristics of HA and, as a result, support longer residence times within joints, and optimize the functionality of viscosupplementation products.

Chemistry and Synthesis Process

  • The research team employed sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(-isopropylacrylamide) in a green chemistry process to develop HA-based polymers. The resulting polymers display spontaneous and reversible formation of nanoparticles at temperatures above 30 degrees Celsius.

Comparison with Existing HA Products

  • The researchers then tested their newly formulated HA polymers against commercially available HA-based viscosupplementation treatments. The new formulations demonstrated significantly greater resistance to both enzymatic and oxidative degradation in vitro, and required only half the force for injection.
  • Furthermore, the novel HA polymers exhibit desirable viscoelastic hydrogel properties in equine synovial fluids, making them potentially more effective in maintaining functional joint movement in treated osteoarthritic patients.

Significance and Implications

  • Altogether, the research work underscores the robust potential of these carefully engineered HA-based systems as future long-lasting viscosupplementation products for patients suffering from osteoarthritis. By improving the stability and functionality of HA-based treatments and easing the process of injection, these new materials could significantly enhance the management and treatment of osteoarthritis.

Cite This Article

APA
Porcello A, Gonzalez-Fernandez P, Jordan O, Allémann E. (2022). Nanoforming Hyaluronan-Based Thermoresponsive Hydrogels: Optimized and Tunable Functionality in Osteoarthritis Management. Pharmaceutics, 14(3). https://doi.org/10.3390/pharmaceutics14030659

Publication

Pharmaceutics
ISSN: 1999-4923
NlmUniqueID: 101534003
Country: Switzerland
Language: English
Volume: 14
Issue: 3

Researcher Affiliations

Porcello, Alexandre
  • School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland.
  • Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1206 Geneva, Switzerland.
Gonzalez-Fernandez, Paula
  • School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland.
  • Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1206 Geneva, Switzerland.
Jordan, Olivier
  • School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland.
  • Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1206 Geneva, Switzerland.
Allémann, Eric
  • School of Pharmaceutical Sciences, University of Geneva, CH-1206 Geneva, Switzerland.
  • Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1206 Geneva, Switzerland.

Conflict of Interest Statement

Authors A.P., O.J. and E.A. were involved in KYLYS Sàrl during the study. The remaining authors declare no conflict of interest.

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