论文标题
用基于透明质酸的纳米水凝胶停止透明质酸酶活性：多功能配方的开发
Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations
论文作者
论文摘要
透明质酸（HA）是用于粘附和化妆品应用的最常用的生物聚合物之一。但是，当前的基于HA的配方具有相关局限性：i）内源性透明质酸酶（HAASE）迅速降解未修饰的HA，从而产生持久的特性； ii）交联的HA，尽管显示出对HAASE的稳定性增强，但通常包含有毒的化学交联。因此，在此，我们提出了生物相容性的自组装透明质酸 - 胆固醇纳米水合凝胶（HA-CH NHS），能够结合到HAASE和抑制体外酶活性，比当前销售的HA基交联配方（例如JonexAtm）更有效地体外酶活性。 HA-CH NHS通过混合机制抑制HAASE，NHS与HAASE结合，亲和力常数比HA高7倍。基于Gellan-胆固醇的类似NHS也证明对HAASE没有任何结合，也不抑制酶活性，这表明这种作用可能是由于HA-CH与酶的活性位点的特异性结合所致。因此，将HA-CH NHS设计为可注射的混合HA混合物或物理水凝胶，能够停止HA的酶促降解。
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.
