Effect of Pulmonary Surfactant and Phospholipid Hexadecanol Tyloxapol on Recombinant Human-Insulin Absorption from Intratracheally Administered Dry Powders in Diabetic Rats

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概要

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• The purpose of the present study was to evaluate the enhancement effect of the natural pulmonary surfactant (PS) or its artificial substitute, phospholipid hexadecanol tyloxapol (PHT) on the bioavailability and hypoglycemic activity of recombinant human insulin (rh-insulin) in a pulmonary delivery system. PS- or PHT-loaded insulin formulation was administered to streptozotocin induced diabetic rats, at doses of 5 U/kg, 10 U/kg and 20 U/kg insulin, respectively. The hypoglycemic effect caused by PS or PHT containing rh-insulin was analyzed and the area above the curves (AAC) of serum glucose levels versus time, the minimum glucose concentration (Cmin), the time to Cmin (Tmin) and the pharmacological availability (PA%) were derived from the serum glucose profiles. Results showed that PS and PHT caused significantly decrease in serum glucose levels. The decrease in plasma glucose levels continued for about 5 h after the nadir. The highest AAC value was obtained when 20 U/kg rh-insulin with PS or PHT as absorption enhancer was administered to rats. AAC0—360 min of PS- or PHT-loaded rh-insulin was 2—3 times as much as that without PS or PHT and PA% increased by 1.3—2 fold. Thus, the extent of oral absorption of insulin from PS- or PHT-loaded particles was significantly greater when compared with that without them. In addition, PHT as well as PS did not change the lactate dehydrogenase (LDH) activity, alkaline phosphatase (AKP) activity and N-acetyl-β-D-glucoaminidase (NAG) activity in bronch fluid which are sensitive indicators of acute toxicity to lung cells in bronchoalveolar lavage (BAL). It is concluded that PS and PHT is a promising absorption enhancer for pulmonary delivery systems of large molecule drugs as rh-insulin.

• 社団法人 日本薬学会の論文

著者

• Zheng Jianheng

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Zhang Ge

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Lu Yang

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Fang Fang

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• He Jiake

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Li Ning

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Talbi Amer

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Zhang Ying

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Tang Yue

  Department of Pharmaceutics, College of Pharmacy, China Pharmaceutical University

• Zhu Jiabi

  Department of Pharmaceutics, College of Pharmacy, China Pharmaceutical University

• Chen Xijing

  Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University

• Zhang Ge

  Center Of Drug Metabolism And Pharmacokinetics Coll. Of Pharmacy China Pharmaceutical Univ.

• Lu Yang

  Center Of Drug Metabolism And Pharmacokinetics Coll. Of Pharmacy China Pharmaceutical Univ.

• Chen Xijing

  Center Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University

• Zhang Ying

  Center Of Drug Metabolism And Pharmacokinetics Coll. Of Pharmacy China Pharmaceutical Univ.

• He Jiake

  Center Of Drug Metabolism And Pharmacokinetics Coll. Of Pharmacy China Pharmaceutical Univ.

• Li Ning

  Center For Non-linear Studies Ms-b258 Los Alamos National Laborator Los Alamos

• Zhang Ying

  Center For Structural And Molecular Biology Institute Of Biophysics Chinese Academy Of Science

関連論文

• Effect of pulmonary surfactant and phospholipid hexadecanol tyloxapol on recombinant human-insulin absorption from intratracheally administered dry powders in diabetic rats
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