Dehydroepiandrosterone in the treatment of steroid resistant asthma: Whether synthetic nanoform can replace the natural hormone?

Efficiency of dehydroepiandrosterone (DHEA) in asthma treatment has been recently shown in multicenter randomized, placebo-controlled trial [1]. But the poor solubility of DHEA and its metabolites restrains the progress in this area. The problem may be resolved by the synthesis of nanoparticles of the hormone using the methods of cryochemical synthesis. The aim of this study was to evaluate peripheral blood lymphocyte (PBL) sensitivity to antiproliferative effect of Dexamethasone (Dx) and DHEA metabolites in asthmatic patients resistant to steroid therapy. Individual PBL susceptibility to Dx and DHEA metabolites including androstendiol (ADL), ADL in the form of nanoparticles (nADL), and β-thiol was evaluated by ED 50 calculation. PBL from both sensitive and resistant patients were investigated. Susceptibility to Dx of sensitive cells was high (ED 50 =8.9 nM); ED 50 for resistant patient was impossible to calculate. However, the cells obtained from resistant patients were sensitive to DHEA metabolites (Table). The data show that DHEA metabolites reveal high anti-proliferative activity against human PBL including the cells isolated from steroid resistant asthmatic patients. Anti-proliferative activities of nADL and β-thiol (the most active but unstable DHEA metabolite) were comparable. It has been noted that nanophorm of the hormone demonstrated higher activity than natural metabolite. Such effect may be explained by the greater bioavailability of nADL. References: 1. Wenzel et al. Allergy Asthma Proc. 2010; 31:461-471.