Alginate aerogels by spray gelation for enhanced pulmonary delivery and solubilization of beclomethasone dipropionate

Abstract

Aerogel technology is an emerging platform that offers alternative and cost-effective dry carriers with advanced performances for the pharmaceutical industry. The innovative combination of compressed air-assisted spray gelation and “green” supercritical fluid (SCF) technology was used in this study to produce alginate aerogel microparticles with adequate properties for pulmonary drug delivery. Beclomethasone dipropionate (BDP), a poorly water-soluble anti-inflammatory drug for asthma treatment, was loaded into alginate aerogel particles by SCF-assisted impregnation ensuring high loading, as well as the amorphization of the drug. The production of aerogels was optimized through the fine-tuning of parameters in compressed air-assisted spray gelation, specifically adjusting the air flow rate and the pump speed. Alginate aerogels were aimed to be produced with an appropriate aerodynamic diameter from 1 to 5 µm, measured by in vitro deposition tests with Next Generation impactor and potential for deep lung penetration. Nuclear magnetic resonance (NMR) relaxometry was used to assess aerogel hydration and unveiled structure–property relationships leading to the sudden release of the drug. Finally, in vitro cytotoxicity tests in fibroblasts and ex vivo permeability tests were conducted. These biological tests confirmed the excellent biocompatibility of the aerogel formulations and demonstrated the efficient deposition of BDP in porcine bronchial tissues assisted by the porous alginate aerogel carrier.