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arXiv · 2206.06110

Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations

E. Montanari·N. Zoratto·L. Mosca·L. Cervoni·E. Lallana·R. Angelini·R. Matassa·T. Coviello·C. Di Meo·P. Matricardi
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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.

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E. Montanari, N. Zoratto, L. Mosca, L. Cervoni, E. Lallana, R. Angelini, R. Matassa, T. Coviello, C. Di Meo, P. Matricardi. 2022-06-13. Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations. https://doi.org/10.1016/j.carbpol.2019.06.004

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