人工肺表面活性物质作为胰岛素肺部给药载体的研究

 目的制备人工肺表面活性物质(APS)作为胰岛素(INS)肺部给药载体。方法在二棕榈酰磷脂酰胆碱(DPPC)中加入脂肪醇、表面活性剂、不饱和磷脂和脂肪酸,制备APS载体。采用脉冲气泡表面张力仪测定APS的最低表面张力,比较不同处方的APS降低表面张力的能力以及INS对APS降低表面张力能力的影响。结果4种APS(DPPC/lecithin-PA,DPPC-Hex-Tyl,DPPC-PG,DPPC/Tyl)的平均最低表面张力分别为9.11,4.10,2.26,1.49 mN·m^-1；INS的加入对APS载体降低表面张力的能力没有显著影响(P＞0.05)；后3种INS-APS制剂具有相似的降低表面张力能力,明显优于DPPC-lecithin-PA-INS制剂(P＜0.01)。4种INS-APS制剂平均粒径范围在0.6～1.8μm之间,符合肺部给药对粒径范围的要求。结论INS不影响APS制剂表面性质,可将APS作为INS肺部给药载体,进一步进行生物有效性和病理学研究。

Primary Study on Artificial Pulmonary Surfactant as Carrier of Insulin Pulmonary Delivery

OBJECTIVE To prepare artificial pulmonary surfactant(APS)as insulin pulmonary delivery agent.METHODS Artificial pulmonary surfactants(DPPC-leeithin-PA,DPPC-Hex-Tyl,DPPC-PG,DPPC-Tyl)were prepared by thin-film suspension method and sonica- tion method.The minimal surface tension of APS was measured by pulsating bubble surface tensioner.The minimal surface tension of APS was compared and the effect of INS on APS was observed.RESULTS The mean minimal surface tension of four kinds of artificial pulmonary,sur-factants(DPPC-lecithin-PA,DPPC-Hex-Tyl,DPPC-PG,DPPC-Tyl)were 9.11,4.10,2.26 and 1.49 mN·m^-1 respectively.The minimal surface tension of latter three APS were similar(P＞0.05)and were much lower than that of DPPC-lecithin-PA(P＜0.01).There was no significant difference in minimal surface tension between APS and INS-APS.The mean particle diameters of INS-APS were 1.71,1.02,1.30 and 0.66μm respectively,which accorded with the particle size range of pulmonary drug delivery.CONCLUSION The result shows that INS has no significant effect on the surface tension of APS.Further research is on the road.