Thiolated human serum albumin cross-linked dextran as a therapeutic hydrogel material

摘要

Hydrogels are poised to play an important role in the delivery of small molecule therapeutics, proteins and cells due to their ability to mimic features of native tissue. We here present a facile and benign method to prepare a hydrogel-based drug delivery system, Dex-sHSA, based on dextran and human serum albumin (HSA) as a dual drug carrier and covalent cross-linker. Binding affinity of the albumin protein for therapeutic cargo was conserved in the thiolation step using 2-iminothiolane and subsequently, in the in situ gelation step by a Michael addition reaction to the dextran polymer scaffold. Oscillation rheometry studies demonstrated the formation of a three-dimensional viscoelastic network upon reaction of dextran and the HSA protein. The mechanical properties of Dex-sHSA hydrogel can be tuned by the protein concentration, and the degree of thiolation of sHSA. Sustained release of hydrophobic drugs such as ibuprofen, paclitaxel and dexamethasone from the Dex-sHSA network were shown over one week. Moreover, the delivery of cancer therapeutics from such scaffolds in the presence of MCF-7 cells was evaluated. This albumin-based dextran hydrogel system demonstrates its potential as a macroscale delivery system of hydrophobic therapeutics for a wide range of biomedical applications.