The effect of injection using narrow-bore needles on mammalian cells: administration and formulation considerations for cell therapies

OBJECTIVES: This study focuses on the effect of the injection administration process on a range of cell characteristics. METHODS: Effects of different ejection rates, needle sizes and cell suspension densities were assessed in terms of viability, membrane integrity, apoptosis and senescence of NIH 3T3 fibroblasts. For ratiometric measurements, a multiplex assay was used to verify cell viability, cytotoxicity and apoptosis independent of cell number. Co-delivery with alginate hydrogels and viscosity-modifying excipients was also assessed. KEY FINDINGS: Ejections at 150 μl/min resulted in the highest percentage of dose being delivered as viable cells among ejection rates tested. The difference in proportions of apoptotic cells became apparent 48 h after ejection, with proportions being higher in samples ejected at slower rates. Co-delivery with alginate hydrogels demonstrated a protective action on the cell payload. CONCLUSIONS: This study demonstrates the importance of careful consideration of administration protocols required for successful delivery of cell suspensions, according to their nature and cellular responses post-ejection.