In vitro characteristics of the human erythrocytes loaded by enalaprilat have been evaluated. Erythrocytes obtained from a healthy volunteer were loaded by enalaprilat using the hypotonic preswelling method, and the loading parameters, drug-release kinetics, hematological indices, particle size distribution, scanning electron microscopy view, osmotic and turbulence fragilities, and deformability of the resulting carrier cells were determined along with the sham encapsulated and unloaded cells. Carrier erythrocytes, having acceptable loading parameters, released their drug content according to zero-order kinetics. Mean corpuscular hemoglobin and mean corpuscular hemoglobin content values of the cells decreased, particle size dispersion increased, the cells transformed to cup-form, the erythrocytes became more fragile against osmotic pressure and turbulent flow, and, finally, the deformability of the cells decreased significantly upon drug loading.

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Inflammatory bowel disease (IBD) is a multifactorial disease with unknown etiology characterized by oxidative stress, leukocyte infiltration, and rise in inflammatory cytokines such as tumor necrosis factor (TNF-alpha). Lithium, as a therapeutic agent for bipolar disorder, exerts some anti-inflammatory properties. In this study we have investigated the effects of lithium on acetic-acid-induced colitis in rats. Lithium (5, 10, and 20 mg/kg) was administered 1 h before the introduction of acetic acid. Colonic status was investigated 24 h following colitis induction through macroscopic, histological, and biochemical analyses. Lithium (20 mg/kg) ameliorated macroscopic and microscopic scores. These observations were accompanied by a reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malondialdehyde content in inflamed colon as well as a decrease in TNF-alpha levels. These findings suggest that lithium exerts beneficial effects on experimental colitis and therefore might be useful in the treatment of IBD.

Encapsulation of drugs in intact erythrocytes, because of the profound characteristics of these natural microspheres, has gained considerable attention in recent years. In this study, the inhibition time courses of serum angiotensin-converting enzyme (ACE) activity after intravenous administration of enalaprilat encapsulated in intact erythrocytes was evaluated and compared with free drug, in a rabbit model. Three groups of animals each received free drug, drug-loaded erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined in each case using the synthetic substrate hippuryl-histidyl-leucine and quantitation of the hippuric acid released by a developed and validated HPLC method. The serum ACE inhibition profiles in the three groups showed that the encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a considerably longer time and in a more reproducible manner, than the free drug or sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as efficacious slow-release drug carriers for enalaprilat in circulation.