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


RESULTS
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.


CONCLUSIONS
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.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Hailong
H
Zhang
Xiaoyan
X
Huang
Jie
J
Mi
Yayu
Y
Huo
Guan
G
Wang
Jianfeng
J
Xing
Yang
Y
Gao
D000818:Animals; D002116:Calcitonin / Q000737:chemistry / Q000493:pharmacokinetics*; D003911:Dextrans / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007328:Insulin / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D008297:Male; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D065589:Respiratory Tract Absorption / Q000187:drug effects*; D013500:Surface Tension
D003911:Dextrans; D007328:Insulin; D004364:Pharmaceutical Preparations; C015219:fluorescein isothiocyanate dextran; C104509:gelucire 44-14; D011092:Polyethylene Glycols; D002116:Calcitonin; D016650:Fluorescein-5-isothiocyanate
Gelucire 44/14; absorption enhancer; membrane toxicity; poorly absorbable drugs; pulmonary absorption