Translational Research
Volume 152, Issue 2 , Pages 59-66, August 2008

In vitro studies of amikacin-loaded human carrier erythrocytes

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain, and Carrier Erythrocyte Research Laboratory, Child Health, Department of Clinical Developmental Sciences, St. George's University of London, London, United Kingdom.

Received 3 March 2008; received in revised form 28 May 2008; accepted 29 May 2008. published online 27 June 2008.

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.

Abbreviations: ANOVA, analysis of variance, MCV, mean corpuscular volume, PBS, phosphate-buffered saline, RES, reticulo-endothelial system

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 Supported by the National Research and Development Plan (Projects SAF 2001-0740 and PI 06152) from the Spanish Government and by a discretionary grant (to B.E.B.).

PII: S1931-5244(08)00153-9

doi:10.1016/j.trsl.2008.05.008

Translational Research
Volume 152, Issue 2 , Pages 59-66, August 2008