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Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice.
Laboratory Animals ( IF 2.4 ) Pub Date : 2020-07-23 , DOI: 10.1177/0023677220939991
Amory L Koch 1 , Milan Rusnak 2 , Katherine Peachee 2 , Akira Isaac 2 , Elizabeth A McCart 2 , W Bradley Rittase 2 , Cara H Olsen 3 , Regina M Day 2 , Aviva J Symes 2
Affiliation  

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these countermeasures utilize murine irradiation models. Yet, the route of drug administration can alter the response to irradiation injury. Studies have demonstrated that cutaneous injuries can exacerbate damage from radiation, and thus surgical implantation of osmotic pumps for drug delivery could adversely affect the survival of mice following TBI. However, daily handling and injections to administer drugs could also have negative consequences. This study compared the effects of subcutaneous needlesticks with surgical implantation of osmotic pumps on morbidity and mortality in a murine model of hematopoietic acute radiation syndrome (H-ARS). C57BL/6 mice were sham irradiated or exposed to a single dose of 7.7 Gy 60Co TBI. Mice were implanted with osmotic pumps containing sterile saline seven days prior to irradiation or received needlesticks for 14 days following irradiation or received no treatment. All irradiated groups exhibited weight loss. Fewer mice with osmotic pumps survived to 30 days post irradiation (37.5%) than mice receiving needlesticks or no treatment (70% and 80%, respectively), although this difference was not statistically significant. However, mice implanted with the pump lost significantly more weight than mice that received needlesticks or no treatment. These data suggest that surgical implantation of a drug-delivery device can adversely affect the outcome in a murine model of H-ARS.



中文翻译:

渗透泵植入与皮下注射给药对小鼠全身照射后给药效果的比较。

核事故或恐怖活动造成辐射暴露的可能性越来越大,因此需要开发针对全身照射 (TBI) 伤害的药物对策。许多开发和测试这些对策的初始实验利用了鼠类辐射模型。然而,给药途径可以改变对辐射损伤的反应。研究表明,皮肤损伤会加剧辐射造成的损伤,因此用于药物输送的渗透泵手术植入可能会对 TBI 后小鼠的存活产生不利影响。然而,日常处理和注射给药也可能产生负面影响。本研究比较了皮下针刺与外科植入渗透泵对造血急性放射综合征 (H-ARS) 小鼠模型的发病率和死亡率的影响。C57BL/6 小鼠被假照射或暴露于 7.7 Gy 的单剂量60 Co TBI。小鼠在照射前 7 天被植入含有无菌盐水的渗透泵,或在照射后接受针刺 14 天或不接受任何治疗。所有照射组均表现出体重减轻。与接受针刺或未接受治疗的小鼠(分别为 70% 和 80%)相比,接受照射后 30 天存活至 30 天的渗透泵小鼠更少(37.5%),尽管这种差异没有统计学意义。然而,植入泵的小鼠比接受针刺或未治疗的小鼠体重明显减轻。这些数据表明,药物输送装置的手术植入会对 H-ARS 小鼠模型的结果产生不利影响。

更新日期:2020-07-24
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