Dicarboxylated hyaluronate: Synthesis of a new, highly functionalized and biocompatible derivative

Sequential periodate-chlorite oxidation of sodium hyaluronate to 2,3-dicarboxylated hyaluronate (DCH), a novel biocompatible and highly functionalized derivative bearing additional pair of -COOH groups at C2 and C3 carbons of oxidized ?-glucuronic acid units, is investigated. The impact of various reaction parameters (time, oxidizer concentration, and molar amount) on DCH's composition, molecular weight, degree of oxidation, and cytotoxicity are investigated to guide the synthesis of DCH derivatives of desired properties. Subsequently, fully (99%) and partially (70%) oxidized DCH derivatives were compared to untreated sodium hyaluronate in terms of anticancer drug cisplatin loading efficacy, carrier capacity, drug release rates, and cytotoxicity towards healthy and cancerous cell lines. DCH derivatives were found to be superior in every aspect, having nearly twice the carrier capacity, significantly slower release rates, and higher efficacy. DCH is thus a highly interesting hyaluronate derivative with an adjustable degree of oxidation, molecular weight, and great potential for further modifications.

Automated summary

The sequential periodate-chlorite oxidation process for the synthesis of 2,3-dicarboxylated hyaluronate (DCH) from sodium hyaluronate is investigated, and the impact of reaction parameters on the properties of DCH is studied. The fully and partially oxidized DCH derivatives are compared to untreated sodium hyaluronate in terms of drug loading efficiency, release rates, and cytotoxicity towards healthy and cancerous cells, and DCH derivatives are found to outperform sodium hyaluronate in all aspects.