School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Dublin, Ireland.
Pharm Res. 2012 Jun;29(6):1425-34. doi: 10.1007/s11095-012-0688-6. Epub 2012 Feb 10.
To investigate DSPE-PEG(2000)-based micellar formulations of salmon calcitonin (sCT) for their ability to improve pulmonary delivery.
Micelles were characterised by DLS and (31)P-NMR spectroscopy. Stability against sCT degrading peptidases, trypsin, α-chymotrypsin and neutrophil elastase as well as their influence on transepithelial absorption was investigated in vitro. In vivo performance of sCT micelles was studied in an experimental model of intratracheal aerosolisation into rats.
Micelles with a mean hydrodynamic diameter of 12 nm spontaneously assembled, when a total concentration of 0.02 mM of PEG-lipid and sCT (at 1:1 molar ratio) was exceeded. Nuclear magnetic resonance confirmed the presence of small micellar structures. The micellar formulation showed increased stability against enzymatic digestion. In vitro studies also showed that sCT micelles were able to enhance transepithelial absorption. Data obtained from in vivo experiments provided evidence of significantly (P < 0.05) higher mean plasma concentrations of sCT, after inhalation of micelles compared to sCT solution, at 60 and 90 min, a significantly higher AUC (inf) and a relative bioavailability of 160 ± 55% when compared to plain sCT solution.
The herein described PEG-lipid micelles are promising carriers for enhanced pulmonary delivery of sCT.
研究基于二硬脂酰基磷脂酰乙醇胺-聚乙二醇（2000）（DSPE-PEG（2000））的鲑鱼降钙素（sCT）胶束制剂提高肺部递药的能力。
采用动态光散射（DLS）和（31）P-NMR 光谱法对胶束进行表征。研究了胶束对 sCT 降解酶（胰蛋白酶、α-糜蛋白酶和中性粒细胞弹性蛋白酶）的稳定性及其对跨上皮吸收的影响。在气管内雾化入大鼠的实验模型中研究了 sCT 胶束的体内性能。
当总浓度为 0.02 mM 的 PEG-脂质和 sCT（摩尔比为 1:1）超过时，胶束的平均水动力直径为 12nm，可自发组装。核磁共振证实了小胶束结构的存在。胶束制剂对酶消化表现出更高的稳定性。体外研究还表明，sCT 胶束能够增强跨上皮吸收。体内实验结果表明，与 sCT 溶液相比，吸入胶束后 60 和 90 分钟时 sCT 的平均血浆浓度显著升高（P<0.05），AUC（inf）显著升高，相对生物利用度为 160±55%。
本文所述的 PEG-脂质胶束是增强 sCT 肺部递药的有前途的载体。
