In vitro studies of amikacin-loaded human carrier erythrocytes
In vitro studies of amikacin-loaded human carrier erythrocytes
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DOI：
10.1016/j.trsl.2008.05.008
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发表时间：
2008-08-01
影响因子：
7.8
通讯作者：
Lanao, Jose M.
中科院分区：
文献类型：
--
作者：
Gutierrez Millan, Carmen;Bax, Bridget E.;Lanao, Jose M.
红细胞包封的抗生素具有提供针对细胞内病原体的有效疗法的潜力。相对于游离抗生素给药的优势包括较低的全身剂量、降低的毒性、以较高浓度持续递送抗生素至病原体复制的细胞内位点以及增加的功效。本研究采用低渗透析法制备人载体红细胞，考察了其对丁胺卡那霉素的包封作用。考察了透析液初始浓度和低渗透析时间对丁胺卡那霉素包封率的影响，并测定了丁胺卡那霉素载体红细胞的渗透脆性和血液学参数。红细胞对丁胺卡那霉素的包封率与药物的初始透析浓度有关。观察到对照和载体红细胞之间的渗透脆性曲线存在统计学显著差异，这取决于低渗透析时间和阿米卡星的透析浓度。评价平均血液学参数，并与未负载的天然红细胞进行比较;丁胺卡那霉素负载载体红细胞的平均红细胞体积（MCV）在统计学上显著较小。阿米卡星表现出持续释放超过48小时的时间内，这表明红细胞作为一个缓慢的系统释放系统的抗生素的潜在用途。
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 carder 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.