A Novel Affinity-Based Controlled Release System Involving Derivatives of Dextran with Enhanced Osmotic Activity

Dextran is a highly biocompatible molecule with osmotic activity. We synthesized histidine derivatives of dextran, DexH (dextran histidine), to test the feasibility of an IMAC-based controlled release system. DexH was synthesized by the periodate oxidation method. The effect of periodate oxidation and histidine conjugation on osmotic activity was tested. The oxidized intermediate itself exhibited higher osmotic activity than native dextran. Conjugation with histidine further increased the osmotic activity, and the resulting DexH exhibited nine times more osmotic activity than native dextran. A positive correlation was observed between the extent of derivatization with histidine and osmotic activity. Association of DexH was tested on two of the matrices, namely, Cu-IDA−Novarose and Zn-IDA−Novarose. DexH bound to both these matrices, and only partial elution was achieved with stepwise lowering of pH, and complete elution was possible only with EDTA. Interestingly, it was found that DexH in its bound state (DexH−Cu-IDA−Novarose and DexH−Zn-IDA−Novarose) exhibited lesser osmotic activity than the eluted soluble form. The IDA-Cu and IDA-Zn-based solid supports bound strongly to DexH in a species-dependent manner, as the IDA-Zn matrix selectively bound DexH with clustered histidine. Further, this DexH with clustered histidine shows higher osmotic activity. A controlled release system is proposed on the basis of this difference in the osmotic activity between the bound and eluted forms of DexH with EDTA as the external trigger to induce this transition in osmotic activity.