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载阿米卡星人载体红细胞的体外研究。

In vitro studies of amikacin-loaded human carrier erythrocytes.

作者信息

Gutiérrez Millán Carmen, Bax Bridget E, Castañeda Aránzazu Zarzuelo, Marinero María Luisa Sayalero, Lanao José M

机构信息

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.

出版信息

Transl Res. 2008 Aug;152(2):59-66. doi: 10.1016/j.trsl.2008.05.008. Epub 2008 Jun 26.

Abstract

Erythrocyte-encapsulated antibiotics have the potential to provide an effective therapy against intracellular pathogens. The advantages over the administration of free antibiotics include a lower systemic dose, decreased toxicity, a sustained delivery of the antibiotic at higher concentrations to the intracellular site of pathogen replication, and increased efficacy. In this study, the encapsulation of amikacin by human carrier erythrocytes prepared using a hypo-osmotic dialysis was investigated. The effects of the initial amikacin dialysis concentration and hypo-osmotic dialysis time on the encapsulation efficiency of amikacin were determined, and the osmotic fragility and hematologic parameters of amikacin-loaded carrier erythrocytes were measured. The efficiency of amikacin entrapment by carrier erythrocytes was dependent on the initial dialysis concentration of the drug. Statistically significant differences in the osmotic fragility profiles between control and carrier erythrocytes were observed, which were dependent on the hypo-osmotic dialysis time and on the dialysis concentration of amikacin. Mean hematologic parameters were evaluated and compared with unloaded, native erythrocytes; the mean corpuscular volume (MCV) of amikacin-loaded carrier erythrocytes was statistically significant smaller. Amikacin demonstrated a sustained release from loaded erythrocytes over a 48-h period, which suggests a potential use of the erythrocyte as a slow systemic-release system for antibiotics.

摘要

红细胞包裹的抗生素有潜力提供针对细胞内病原体的有效治疗方法。相较于使用游离抗生素给药,其优势包括更低的全身剂量、更低的毒性、以更高浓度持续将抗生素递送至病原体复制的细胞内位点以及更高的疗效。在本研究中,对使用低渗透析制备的人载体红细胞包裹阿米卡星进行了研究。测定了初始阿米卡星透析浓度和低渗透析时间对阿米卡星包裹效率的影响,并测量了负载阿米卡星的载体红细胞的渗透脆性和血液学参数。载体红细胞对阿米卡星捕获的效率取决于药物的初始透析浓度。观察到对照红细胞和载体红细胞之间的渗透脆性曲线存在统计学上的显著差异,这取决于低渗透析时间和阿米卡星的透析浓度。评估了平均血液学参数并与未负载的天然红细胞进行比较;负载阿米卡星的载体红细胞的平均红细胞体积(MCV)在统计学上显著更小。阿米卡星在48小时内从负载的红细胞中持续释放,这表明红细胞有潜力作为抗生素的缓慢全身释放系统。

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