Incorporation of Beclomethasone Dipropionate into Polyethylene Glycol-Diacyl Lipid Micelles as a Pulmonary Delivery System

Nebulized corticosteroid drugs have several shortcomings due to their poor water solubility and nonoptimal deposition pattern. The aims of this study were to investigate the in vitro and in vivo characteristics of beclomethasone dipropionate (BDP)-loaded sterically stabilized phospholipid nanomicelles (SSMs) of a polyethylene glycol-phosphatidylethanolamine conjugate as a pulmonary delivery system. The particle size distribution and zeta potential measurements were 14.60 +/- 1.11 nm and -46.94 +/- 3.27 mV, respectively. The solubility of BDP was highly improved by at least 1,300 times its actual solubility. No chemical interaction was found between the PEGylated polymer and BDP as demonstrated by the Fourier transform infrared results. The in vitro aerodynamic of the aerosolized BDP-SSMs using an Omron nebulizer showed an improvement in the aerodynamic values, with a significant deposition in the seven-stage Next Generation Impactor. The BDP-SSMs showed a prolonged dissolution profile of about 3 days. Intratracheal administration of the BDP-SSMs (1 mg/ kg) 12 or 23 h before a challenge in the asthmatic rat model led to a significant reduction in the inflammatory cell counts in bronchoalveolar lavage fluid samples compared with the administration of solubilized BDP. The SSM system appears to be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids. Drug Dev Res 73: 90-105, 2012. (C) 2011 Wiley Periodicals, Inc.