Inhaled insulin is better absorbed when administered as a dry powder compared to solution in the presence or absence of alkylglycosides.
Inhaled insulin is better absorbed when administered as a dry powder compared to solution in the presence or absence of alkylglycosides.
复制标题
与存在或不存在烷基糖苷的溶液相比，以干粉形式施用的吸入胰岛素吸收更好。
DOI：
10.1007/s11095-005-8926-9
复制
发表时间：
2006
影响因子：
3.7
通讯作者：
Ahsan,Fakhrul
中科院分区：
文献类型：
--
作者：
Hussain,Alamdar;Majumder,QuamrulH;Ahsan,Fakhrul
目的研究不同烷基链长的烷基糖苷经呼吸道给药的安全性，并比较胰岛素作为干粉吸入剂和吸入剂后在肺内的吸收情况。方法通过测定大鼠肺泡灌洗液中的酶活性，研究不同烷基链长的烷基糖苷的安全性。将胰岛素和辛基麦芽糖苷组成的肺制剂分别以溶液和冻干粉剂的形式给予麻醉大鼠，通过测定血浆胰岛素和血糖水平来评估胰岛素的吸收。结果BAL分析显示，随着烷基糖苷疏水链长的增加，肺损伤标志物的释放量逐渐增加。胰岛素+辛基麦芽糖苷冻干粉或其溶液制剂的肺给药结果表明，粉剂的生物利用度比以溶液形式给药的高约2倍。扫描电子显微镜研究表明，冻干后的制剂颗粒表面形态略有不同。FTIR数据显示，在冻干过程中，多肽与辅料之间的相互作用很小。结论在所测试的烷基糖苷中，辛基麦芽糖苷释放肺损伤标志物的毒性最小。以辛基麦芽糖苷为基础的干粉胰岛素制剂与溶液制剂相比，在促进肺胰岛素吸收和降低血糖水平方面更有效。
PurposeThis study was performed to investigate the safety of alkylglycosides administered via the respiratory route and to compare the pulmonary absorption profiles of insulin administered as dry powder inhaler and inhaler solution.MethodsThe safety of a series of alkylglycosides with varying alkyl chain lengths was studied by measuring the enzymatic activities in the bronchoalveolar lavage (BAL) fluid of rat lungs. Pulmonary formulations of insulin plus octylmaltoside were administered either as solution or lyophilized dry powder to anesthetized rats, and absorption of insulin was assessed by measuring plasma insulin and glucose levels. The physical characterization of the dry powder formulation was performed using scanning electron microscope (SEM) and Fourier transform infrared spectrophotometer (FTIR).ResultsThe BAL analysis showed that there was a gradual increase in the amount of lung injury markers released with the increase in the hydrophobic chain length of alkylglycosides. The pulmonary administration of lyophilized dry powder of insulin plus octylmaltoside or its solution counterpart showed that the bioavailability of powder formulation was about 2-fold higher than that of the formulation administered as solution. The SEM studies showed a subtle difference in the surface morphologies of formulation particles after lyophilization. FTIR data showed minor interactions between the peptide and excipients upon lyophilization.ConclusionsOf the alkylglycosides tested, octylmaltoside was least toxic in releasing lung injury markers. Octylmaltoside-based dry powder insulin formulations were more efficacious in enhancing pulmonary insulin absorption and reducing plasma glucose levels compared with the formulations administered as a solution.