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首页> 外文期刊>Journal of Pharmacological and Toxicological Methods >Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein
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Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein

机译：猪模型评估与皮下递送蛋白质相关的局部组织耐受性

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Introduction: The conversion from intravenous (IV) to subcutaneous (SC) delivery of biotherapeutics has increased in recent years. Some of the reasons for this shift in route of delivery are due to patient convenience, reduced adverse systemic effects, lack of a need for vascular access, and reduced cost of patient care, which ultimately lead to improved patient quality of life. One caveat to SC delivery is the limited volumes that can be administered at a single site and the associated local tolerability. To characterize factors that affect subcutaneous delivery of large volumes of therapeutic proteins, a porcine model was developed. Model endpoints included measurement of interstitial pressure, assessment of local skin visco-elasticity, and the qualitative assessment of local infusion sites. Methods: Immunoglobulin G (IgG) was subcutaneously infused into the abdominal region of Yucatan miniature swine. Changes in interstitial pressure were measured, using an in-line pressure transducer, during and after infusions. Additionally, pre- and post-infusion changes in local skin visco-elasticity were measured using a Cutometer?. Lastly, infusion sites were assessed for post-infusion local skin reactions such as erythema and swelling. Similar assessments were made following SC IgG delivery with the permeation enhancer recombinant human hyaluronidase PH20 (rHuPH20). Results: Subcutaneous infusions of IgG, in the presence of rHuPH20, significantly reduced average interstitial pressures by 55% during the infusion period and by 67% during the post-infusion period, compared to the control. Infusions in the presence of rHuPH20 also maintained better local skin elasticity as seen by a 42% increase in local skin pliability compared to the control. Finally, infusions with rHuPH20 resulted in an 80% reduction in swelling area compared to the control. Discussion: A large animal model was developed that incorporates both quantitative and qualitative assessment methods to aid in understanding SC delivery of proteins.
机译：简介：近年来，从静脉内（IV）到皮下（SC）递送的静脉内（SC）递送。交付途径的一些原因是由于患者的便利性，减少了不良的全身效应，缺乏血管进入的需求，并且减少患者护理的成本，最终导致患者生活质量提高。一个警告到SC递送是可以在单个网站和相关的局部耐受性施用的有限体积。表征影响大量治疗蛋白的皮下递送的因素，开发了一种猪模型。模型终点包括间质压力，局部皮肤粘弹性评估以及局部输注位点的定性评估。方法：将免疫球蛋白G（IgG）皮下注入尤卡坦微型猪的腹部地区。测量间质压的变化，使用在线压力传感器，期间和输注后。另外，使用测光仪测量局部皮肤粘弹性的预灌注后和输注后变化？最后，评估输液位点用于输注后局部皮肤反应，例如红斑和肿胀。通过渗透增强剂重组人透明质酸酶pH20（rhuph20），使SC IgG递送等类似的评估。结果：与对照相比，在rhuph20的存在下，在rhuph20的存在下，在rhuph20的存在下显着降低了55％的平均间质压力为55％，与对照期间的输注后的67％。 rhuph20存在下的输注也保持了更好的局部皮肤弹性，与对照相比，局部皮肤宽度的增加42％。最后，与rhuph20的输注导致膨胀区域减少80％，与对照相比。讨论：开发了大型动物模型，其包括定量和定性评估方法，以帮助了解蛋白质的SC递送。

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