Use of encapsulated dexamethasone sodium phosphate (eDSP) in chronic obstructive pulmonary disease, cystic fibrosis, and inflammatory bowel disorders.

Abstract

Glucocorticoids are cornerstone treatment for inflammatory diseases but are limited by systemic toxicity from high-dose and prolonged use. Encapsulation of dexamethasone sodium phosphate (DSP) in autologous erythrocytes aims for sustained drug release with an improved safety profile. This manuscript summarizes early clinical studies of encapsulated DSP (eDSP) in pulmonary and inflammatory bowel disorders (IBD). From 2001 to 2013, eight clinical studies investigated eDSP in patients whose age ranged from 5 to 83 years, with chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), Crohn's disease (CD), and ulcerative colitis (UC). DSP was loaded into autologous erythrocytes ex vivo and reinfused every 2 weeks, or monthly. Follow-up ranged from 1 to 24 months. In pulmonary indications, eDSP resulted in improved FEV1 and reduced infections in CF patients, and improved symptoms in COPD with markedly reduced corticosteroid doses. In IBD, eDSP enabled steroid withdrawal in 60%-78% of patients and achieved remission in pediatric and adult CD and UC. Adverse effects typical of corticosteroids were notably absent. Limitations of these studies included small sample sizes, lack of placebo groups in some trials, and inter-patient variability in erythrocyte drug loading. Pharmacokinetic studies documented persistence of dexamethasone levels up to 4 weeks post-infusion. Early studies demonstrate that eDSP is a feasible and well-tolerated treatment in children and older patients, delivering low-dose corticosteroids with prolonged therapeutic levels. These findings support further development of erythrocyte-based drug delivery for chronic inflammatory diseases in patients with steroid sensitive or steroid-dependent disease.