Inkjet-printed alginate microspheres as additional drug carriers for injectable hydrogels

Local delivery of bioactive molecules to the inner ear via diffusion through the round window membrane is becoming an attractive approach to treat sensorineural hearing loss compared to systemic drug administration. Pluronics® (Lutrol F127) are a class of thermosensitive hydrogels that remain liquid prior to injection and rapidly gel under physiological conditions. They are, however, limited to short-term drug release due to rapid hydrolysis in aqueous solution. Therefore, the aim of this study was to investigate an approach, using an ink-jet printing system, to sustain the drug release by incorporating hydrogel microspheres within Lutrol F127. Various concentrations of Lutrol F127 and calcium chloride (CaCl2) were examined by rheology to determine the optimum combinations to use for injection and then blended with inkjet-printed alginate microspheres. Drug release (FITC-Dextran) from Lutrol F127 alone reached completion in less than 24 h. Release from alginate spheres alone showed a burst release and reached 100% in 6 h. Interestingly, the incorporation of microspheres within Lutrol F127 allowed a more sustained release profile and a slower burst release. By varying the quantity of microspheres, concentration of alginate, or ionic cross-linking ratio, the release profile can be adjusted to suit the desired application.