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

Abstract

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.