Characterization and evaluation of β-glucan formulations as injectable implants for protein and peptide delivery.

CONTEXT Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature. OBJECTIVE To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG. MATERIALS AND METHODS Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G") moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells. RESULTS Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p < 0.001) from 3.65 ± 0.43 to 34.30 ± 8.90 (dextran) and 805.80 ± 5.30 (PEG) 24 h after polymer addition. In vitro release profiles showed significantly (p < 0.05) reduced AUC(0-8 h), k and percentage of drug released from two-phase systems compared to β-glucan dispersions, with the PEG system resulting in the lowest amount released over 8 h (15.1 ± 1.6%). DISCUSSION The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense β-glucan gel. CONCLUSION 1.5% (w/w) β-glucan combined with PEG at a ratio of 1:3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release.