Preparation and in-vitro characterization of tramadol-loaded carrier erythrocytes for long-term intravenous delivery

Abstract

Objectives: The hypo-osmotic dialysis method was used for preparation of tramadol-loaded human intact erythrocytes. In response to rapid drug escape from the erythrocytes, a membrane cross-linker, glutaraldehyde, was used successfully. Methods: The resulting carrier cells were validated in terms of the accuracy and precision of the whole drug loading procedure. Key findings: The average loaded amount, entrapment efficiency and cell recovery were 1.9041 mg, 95.98% and 85.13%, respectively. The effects of different drug concentrations on loading parameters were studied with the concentration of 10 mg/ml selected as optimal. A series of in-vitro characteristics of carrier erythrocytes, including tramadol release behaviour, haematological indices, particle size distribution, scanning electron microscopy, and osmotic/turbulence fragilities were determined compared with the sham-entrapped and unloaded cells. The results of these in-vitro tests indicated that the erythrocytes did not undergo remarkable irreversible size and shape/topology changes, but the fragility of the membranes of the processed cells were increased. Conclusions: The collective results of this study showed that the optimized method of entrapment was suitable for the encapsulation of tramadol in erythrocytes with the final carrier cells ready to enter the in-vivo animal studies as a promising long-circulating carrier for tramadol. © 2010 The Authors JPP © 2010 Royal Pharmaceutical Society.