1. Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations
- Author
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Montanari, E., Zoratto, N., Mosca, L., Cervoni, L., Lallana, E., Angelini, R., Matassa, R., Coviello, T., Di Meo, C., and Matricardi, P.
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Condensed Matter - Soft Condensed Matter - Abstract
Hyaluronan (HA) is among the most used biopolymers for viscosupplementation and cosmetic applications. 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. JonexaTM). 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 HA. Similar NHs, based on gellan-cholesterol, 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., Comment: 27 pages, 9 figures
- Published
- 2022
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