Wenzhou Medical College, Wenzhou, Zhejiang Province, China.
Diabetes Technol Ther. 2011 Jul;13(7):759-65. doi: 10.1089/dia.2010.0231. Epub 2011 Apr 21.
The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.
Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption.
Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively.
Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.
本研究旨在探讨脂质体和微泡在胰岛素肺部吸收中的增强效率。
制备了两种基于磷脂的囊泡-脂质体和微泡，并使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）细胞毒性试验评估其在 A549 细胞中的体外毒性。使用 A549 细胞测定胰岛素与脂质体或微泡结合后的细胞摄取率。通过气管内滴注 Sprague-Dawley 大鼠，给予胰岛素与脂质体或微泡的混合物，以评估其促进药物肺部吸收的潜力。
脂质体和微泡的粒径分布均较窄且单分散，平均直径分别为 3.1μm 和 1.0μm。从 MTT 细胞毒性试验来看，最终体积中磷脂基囊泡浓度<25%（体积/体积）是避免严重细胞毒性作用的安全剂量范围。胰岛素-微泡混合物中胰岛素的细胞内摄取量明显高于胰岛素-脂质体混合物。胰岛素-微泡和胰岛素-脂质体混合物使血糖浓度的最小降低分别为初始葡萄糖水平的 60.8%和 35.0%，其相对于皮下注射的生物利用度分别为 48.6%和 30.8%。
微泡在胰岛素肺部吸收的速率和程度方面比脂质体具有更高的效率。微泡可能被推荐作为增强蛋白质肺内吸收的潜在药物。
