Preparation and characterization of a novel pH-sensitive Salecan-g-poly(acrylic acid) hydrogel for controlled release of doxorubicin.

Abstract

Salecan is a novel water-soluble extracellular β-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09. Salecan is suitable for the fabrication of hydrogels for biomedical applications due to its excellent physicochemical and biological properties. In this paper, a series of pH-sensitive hydrogels were prepared in aqueous solution by the graft copolymerization of Salecan and acrylic acid (AA) using N,N'-methylene diacrylamide as a crosslinker for controlled drug delivery. The structure and thermal stability of the resulting hydrogels were characterized by FT-IR, XRD and TGA. By SEM analysis, freeze-dried hydrogels displayed an interconnected porous structure with tunable pore size in the range of 23.2-90.3 μm. The swelling behavior of the hydrogels was shown to be highly dependent on the environmental pH, salt type and concentration, as well as the contents of Salecan and BAAm. They are almost unswellable at pH 1.2 and swollen extensively at pH 6.86. Meanwhile, the increase in the content of hydrophilic Salecan could enhance the swelling ratio, whereas the presence of more BAAm reduced the swelling capacity but promoted the water retention to some extent. Rheological tests revealed that storage modulus G' was strongly influenced by the crosslink density of the obtained hydrogel network. Especially, doxorubicin (DOX) as a model anti-cancer drug was very efficiently loaded into the negatively charged hydrogels (up to 69.4 wt%) through electrostatic interactions. More importantly, the release of DOX from this intelligent system exhibited pH-responsive behavior and a sustained release pattern. For SPA2, the cumulative release profile showed a low level of drug release (about 12.3 wt% in 24 h) at pH 7.4, and was significantly accelerated at pH 4.0 (over 40 wt% in 6 h). Cytotoxicity experiments confirmed that all blank hydrogels were non-toxic to A549 cells, while DOX released from the drug-loaded hydrogels remained biologically active and had the capability to kill cancer cells. The preliminary results clearly suggested that the Salecan-g-PAA hydrogels may be promising carriers for controlled drug delivery.