Calcium ion cross-linking alginate/dexamethasone sodium phosphate hybrid hydrogel for extended drug release

Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH (e.g., its low mechanical property) and is associated with the enhancement of materials performance, which is useful in a variety of biomedical applications. In the present work, a hybrid hydrogel that combines dexamethasone sodium phosphate (Dexp) and a polysaccharide (alginate) was explored via a calcium ion coordination strategy. With the addition of Ca²⁺ to an aqueous solution of Dexp/alginate, the Ca²⁺/Dexp/alginate hybrid hydrogel formed spontaneously. The formed Ca²⁺/Dexp/alginate hybrid hydrogels were thoroughly characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). An in vitro drug release study indicated that the formed Ca²⁺/Dexp/alginate hybrid hydrogel provided a slower drug release rate than did the Ca²⁺/Dexp hydrogel, and the drug release behaviour could be finely tailored by the change of Ca²⁺ concentration. More importantly, the subcutaneous injection of the Ca²⁺/Dexp/alginate hybrid hydrogel significantly extended the in vivo retention of the hydrogel in situ compared to that of the Ca²⁺/Dexp hydrogel. The in vivo pharmacokinetic analysis indicated that the Ca²⁺/Dexp/alginate hybrid hydrogel could greatly extend drug release in vivo and significantly improve drug bioavailability compared to the Ca²⁺/Dexp hydrogel. As such, the formed Ca²⁺/Dexp/alginate hybrid hydrogel combined the greater resilience of an alginate network with the long in vivo duration of a low-molecular-weight hydrogel (Ca²⁺/Dexp hydrogel) and remarkably enhanced drug bioavailability, which might open an avenue for the design of self-assembling steroidal drug-polysaccharide hybrid hydrogels for drug delivery applications.