Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations. (1st October 2019)

• Record Type: Journal Article
• Authors: Montanari, E.; Zoratto, N.; Mosca, L.; Cervoni, L.; Lallana, E.; Angelini, R.; Matassa, R.; Coviello, T.; Di Meo, C.; Matricardi, P.
• Is Part Of: Carbohydrate polymers. Volume 221(2019)
• Page Start: 209
• Page End: 220
• Publication Date: 2019-10-01
• Subjects: HA hyaluronan -- HAase hyaluronidase -- HA-CH hyaluronan-cholesterol -- Ge-CH gellan-cholesterol -- NHs nanohydrogels -- PHs physical hydrogels -- HHs hybrid hyaluronan mixtures -- Hylastan Jonexa™ Hylastan SGL-80 -- OA osteoarthritis; Nanohydrogels -- Hyaluronidase inhibitor -- Hyaluronan-cholesterol -- Viscosupplementation -- Dermal filler; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2019.06.004
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Hyaluronan-cholesterol nanohydrogels inhibit hyaluronidase activity, halting the enzymatic degradation of hyaluronan. Hyaluronan-cholesterol nanohydrogels bind to hyaluronidase with an affinity constant higher than that of hyaluronan. Development and characterisation of versatile hyaluronidase-resistant injectable mixtures for viscosupplementation and dermo-cosmetic applications. Abstract: Hyaluronan (HA) is among the most used biopolymers for viscosupplementation and dermocosmetics. However, the current injectable HA-based formulations present relevant limitations: I) unmodified HA is quickly degraded by endogenous hyaluronidases (HAase), resulting in short lasting properties; II) cross-linked HA, although shows enhanced stability against HAase, often contains toxic chemical cross-linkers. As such, herein, we present biocompatible self-assembled hyaluronan-cholesterol nanohydrogels (HA-CH NHs) able to bind to HAase and inhibit the enzyme activity in vitro, more efficiently than currently marketed HA-based cross-linked formulations ( e.g. Jonexa™). HA-CH NHs inhibit HAase through a mixed mechanism, by which NHs bind to HAase with an affinity constant 7-fold higher than that of native HA. Similar NHs, based on gellan-CH, evidenced no binding to HAase, neither inhibition of the enzyme activity, suggesting this effect might be due to the specific binding of HA-CH to the active site of the enzyme. Therefore, HA-CH NHs were engineered into injectable hybrid HA mixtures or physical hydrogels, able to halt the enzymatic degradation of HA.