Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin
Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin
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DOI：
10.1080/03639045.2017.1353521
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发表时间：
2017-01-01
影响因子：
3.4
通讯作者：
Itagaki, Shirou
中科院分区：
文献类型：
--
作者：
Chono, Sumio;Togami, Kohei;Itagaki, Shirou
目的：我们之前的研究表明，含有双棕榈酰磷脂酰胆碱（DPPC）的雾化脂质体可以增强包封胰岛素的肺部吸收。在这项研究中，我们的目的是比较胰岛素包封在脂质体与空脂质体和未包封的游离胰岛素，其中DPCC脂质体将作为吸收促进剂。意义：本研究为糖尿病无创治疗的发展提供了有益的信息。方法：在体内研究空DPPC脂质体与未包封的游离胰岛素共同给药对蛋白质肺吸收的潜在增强作用。联合给药与包封胰岛素的DPPC脂质体和游离胰岛素比较。结果：DPPC脂质体增强了未包封游离胰岛素的肺吸收；但与包封胰岛素的DPPC脂质体相比，其增强作用较弱。DPPC脂质体对未包封的游离胰岛素的肺吸收机制与包封胰岛素的DPPC脂质体类似，其机制为肺泡粘膜上皮细胞间隙的打开，而非粘膜细胞损伤。在体外稳定性试验中，覆盖上皮细胞的肺泡黏液层中的胰岛素是稳定的。这些结果表明，尽管未包封的游离胰岛素在肺泡黏液层中扩散，但胰岛素被包封到DPPC脂质体中，可以增加吸收表面附近释放的胰岛素浓度，同时也提高了吸收效率。结论：胰岛素包封在DPPC脂质体中比DPPC脂质体和未包封的游离胰岛素同时给药更有效地促进肺部胰岛素吸收。
Objective: We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer.Significance: The present study provides the useful information for development of noninvasive treatment of diabetes.Methods: Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin.Results: DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased.Conclusion: We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.