The effect of injection using narrow-bore needles on mammalian cells: administration and formulation considerations for cell therapies.
The effect of injection using narrow-bore needles on mammalian cells: administration and formulation considerations for cell therapies.
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DOI：
10.1111/jphp.12362
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Shakesheff KM
中科院分区：
文献类型：
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作者：
Amer MH;White LJ;Shakesheff KM
本研究的重点是注射给药过程对一系列细胞特性的影响。在NIH 3 T3成纤维细胞的活力、膜完整性、凋亡和衰老方面评估不同喷射速率、针尺寸和细胞悬液密度的影响。对于比率测量，使用多重测定来验证细胞活力、细胞毒性和细胞凋亡，而不依赖于细胞数量。还评估了与藻酸盐水凝胶和粘度改性赋形剂的共递送。以150 μl/min喷射导致在所测试的喷射速率中以活细胞形式递送的剂量百分比最高。凋亡细胞比例的差异在喷射后48小时变得明显，在以较慢速率喷射的样品中比例较高。与藻酸盐水凝胶的共递送证明了对细胞有效载荷的保护作用。本研究证明了根据细胞悬液的性质和排出后的细胞反应，仔细考虑成功递送细胞悬液所需的给药方案的重要性。
This study focuses on the effect of the injection administration process on a range of cell characteristics. 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. 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. 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.