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Preparation of Hydroxy-PAAm Hydrogels for Decoupling the Effects of Mechanotransduction Cues
Published on: August 28, 2014
DIC/Oxyma as efficient amide coupling agent for synthesis of amphiphilic hyaluronic acid conjugates in co-solvent
Prasanna Wijerathna1, You-Sin Jian1, Chih-An Lin2
1Department of Chemistry, National Chung Hsing University, Taichung, 402, Taiwan.
Abstract:
Carbohydrate polymers are often sought for the fabrication of self-assembling nanocarriers of varying architecture through chemical modification involving physiologically stable amide bonds, predominantly via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC)/N-hydroxysuccinimide (NHS) click reactions. However, the degree of substitution (DS) or conjugation efficiency (CE) of EDC/NHS in reactions involving co-solvent systems is quite low. Thus, safe and effective amide coupling agents that can foster the conjugation of hydrophobic moieties with water-soluble carbohydrate polymers such as hyaluronic acid (HA) without the need for pre-modification are in ultimatum. This study aimed to optimize the CE of diisopropylcarbodiimide (DIC)/ethyl 2-cyanohydroxyiminoacetate (Oxyma) in co-solvent system and compare with EDC/NHS and DIC/1-hydroxybenzotriazole (HOBt) in the conjugation of HA with model hydrophobic drugs, nimesulide (NIM), lenalidomide (LEN), and estradiol (E2). Intriguingly, DIC/Oxyma had higher CE in the synthesis of HA-NIM (97.80%), HA-LEN (62.30%), and HA-β-Ala-E2 (24.00%) compared to EDC/NHS and DIC/HOBt in similar co-solvent system (ddH2O/DMSO, 2:3). Unlike the EDC/NHS characterized by Loosen rearrangements, the DIC/Oxyma coupling reaction didn't foster formation of side products and alter the molecular weight of HA. In addition, the desirable CE of DIC/Oxyma shown to be consistent across different molecular weight HA. In summary, the observed high CE of DIC/Oxyma in co-solvent systems reiterates its importance in the conjugation of carbohydrate polymers intended to ameliorate the pharmacokinetic properties of hydrophobic drugs.
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