Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations.
Halting hyaluronidase activity with hyaluronan-based nanohydrogels: development of versatile injectable formulations.
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DOI：
10.1016/j.carbpol.2019.06.004
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发表时间：
2019-10
影响因子：
11.2
通讯作者：
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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文献类型：
--
作者：
E. Montanari;N. Zoratto;L. Mosca;L. Cervoni;E. Lallana;R. Angelini;R. Matassa;T. Coviello;C. Di Meo;P. Matricardi
透明质酸 (HA) 是最常用于粘稠补充和皮肤化妆品的生物聚合物之一。然而，目前基于HA的注射制剂存在相关局限性：I)未修饰的HA会被内源性透明质酸酶(HAase)快速降解，导致特性持续时间短； II) 交联的HA虽然对HAase表现出增强的稳定性，但通常含有有毒的化学交联剂。因此，本文中，我们提出了生物相容性自组装乙酰透明质酸-胆固醇纳米水凝胶（HA-CH NH），能够与HAase结合并在体外抑制酶活性，比目前市售的基于HA的交联制剂（例如Jonexa™）更有效。 HA-CH NHs 通过混合机制抑制 HAase，NHs 与 HAase 的结合亲和力常数比天然 HA 高 7 倍。类似的基于结冷胶-CH的NHs没有与HAase结合，也没有抑制酶活性，表明这种效应可能是由于HA-CH与酶活性位点的特异性结合所致。因此，HA-CH NHs被设计成可注射的混合HA混合物或物理水凝胶，能够阻止HA的酶促降解。
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 activityin 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.