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 (TM)). 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.
Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations
Angelini R.;
2019
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 (TM)). 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.File | Dimensione | Formato | |
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Descrizione: Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations
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Descrizione: Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations
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