Erythrocytes-mediated delivery of dexamethasone in steroid-dependent IBD patients - A pilot uncontrolled study

BACKGROUND AND AIM: Autologous erythrocytes can be used as carriers of drugs, owing to the ability of their membrane to be opened and resealed under appropriate conditions. In this pilot uncontrolled study, we investigated efficacy and safety of dexamethasone-encapsulated erythrocytes in steroid-dependent IBD patients. MATERIALS AND METHODS: Ten patients (5 with ulcerative colitis and 5 with Crohn's disease) with steroid dependency ranging from 8 to 60 months were studied. Seven of them were in clinical remission, and the remaining three had mild activity. Eight patients were also under azathioprine or 6-MP for at least 6 months (range 6-24 months), while another two patients were intolerant to both drugs. Fifty milliliters of blood were drawn from each subject; dexamethasone 21-Phosphate (Dex 21-P) was encapsulated into erythrocytes by means of specially designed equipment, and drug-loaded erythrocytes were infused into original donors. The procedure was repeated after 4 and 8 wk, and patients were instructed to withdraw corticosteroids. RESULTS: A mean dose of 5.5 +/- 2.4 mg Dex 21-P was loaded in the erythrocytes at each treatment. Following re-infusion of loaded erythrocytes, plasma Dexamethasone (Dex) concentrations were detected after as long as 28 days. Steroids were completely withdrawn by the second month. After the third infusion, all patients, including the three with mild active disease, were in clinical remission. ESR levels dropped from 47 +/- 27 at baseline to 27 +/- 16 mm/h (p < 0.02), and CRP levels from 1.6 +/- 1.3 to 0.6 +/- 0.5 mg/dl (p < 0.02). After a mean follow-up of 12 +/- 3 months, six patients relapsed, and the remaining four patients remained in remission. Pre-existing steroid-related adverse effects disappeared during the follow-up. CONCLUSIONS: Loading of Dex 21-P in autologous erythrocytes is feasible and safe. The very low dose of Dex released in blood stream was able to maintain patients in clinical remission and allowed steroids withdrawal.