Development of an injectable, in situ formed hydrogel for controlled release of local anesthetics

Injectable hydrogels are recognized as interesting delivery systems for local anesthetics. Calcium-alginate is expected to have particularly high potential due to the well-documented biocompatibility and the assumed beneficial effect on neural tissue. Formulating an injectable calcium-alginate hydrogel is complex since the phase transition and the mechanical properties may be changed by specific drug molecules. The purpose of this study was to investigate possibilities for encapsulating lidocaine, with the focus on tuning the gelling kinetics and the viscoelastic properties to achieve gelling time between 1 and 2 min followed by controlled drug release. Rheological analysis identified the [Ca²⁺]/[COO⁻] ratio as the key factor that could be manipulated to fine-tune both the gelling time and the crosslinking density. By lowering the ratio from 15 to 10, the gelling time was prolonged from 1.61 to 2.63, and from 1.57 to 2.78 min, for 1 % (w/v) and 1.5 % (w/v) alginate, respectively. In the presence of lidocaine, the gelling times were reduced, resulting in <0.75–0.95 min for 1 % (w/v), and 1.02–1.68 min for 1.5 % (w/v) alginate. The accompanying decreases in storage moduli by lowering the ratio from 15 to 10 were almost 90 % in the drug-free formulations, and about 60 % in the presence of drug. Lidocaine affected the storage moduli in formulations with high ratio by reducing them by about 50 %. Despite the apparently reduced crosslinking density, the investigated gels displayed favorable mechanical properties and drug retention capacity, with about 80 % of lidocaine being released by Fickian diffusion during 8 h.