Improvement of pulmonary absorptions of poorly absorbable drugs using Gelucire 44/14 as an absorption enhancer

Abstract

Abstract Objectives This study aims to evaluate the absorption-enhancing effects of Gelucire 44/14 on the pulmonary absorption of different poorly absorbable drugs and relative mechanism of action. Methods Absorption-enhancing effect of Gelucire 44/14 were examined by an in-vivo pulmonary absorption experiment in rats, and the membrane toxicity of Gelucire 44/14 was evaluated by measuring levels of protein and dehydrogenase (LDH) in the bronchoalveolar lavage fluid (BALF) and morphological observation. Key findings Pulmonary absorptions of fluorescein isothiocyanate-dextrans, insulin and calcitonin were enhanced by Gelucire 44/14 (0.1–2.0%, w/v) in a concentration-dependent manner, and the maximal absorption-enhancing effect was obtained when the concentration of Gelucire 44/14 increased to 2.0% (w/v). Furthermore, Gelucire 44/14 neither increase the levels of protein and LDH in BALF nor change morphology of lung compared with control group. In addition, a well correlation between the absorption-enhancing effect and surface tension of insulin solution in the presence of Gelucire 44/14 was observed, suggesting Gelucire 44/14-mediated decrease in the surface tension of the gas-liquid interface in alveolar tissue was possible one of the improving mechanisms of Gelucire 44/14. Conclusion Gelucire 44/14 was a potential and safe absorption enhancer for improving the absorption of poorly absorbable drugs including insulin and calcitonin by pulmonary delivery.