Edwards D A, Hanes J, Caponetti G, Hrkach J, Ben-Jebria A, Eskew M L, Mintzes J, Deaver D, Lotan N, Langer R
Department of Chemical Engineering, Pennsylvania State University, 204 Fenske Laboratory, University Park, PA 16802, USA.
Science. 1997 Jun 20;276(5320):1868-71. doi: 10.1126/science.276.5320.1868.
A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.
一种新型吸入气雾剂,其特点是质量密度小且颗粒尺寸大,能使吸入疗法药物高效进入体循环。质量密度小于0.4克每立方厘米且平均直径超过5微米的颗粒可深入肺部,避开肺部的自然清除机制,直至吸入颗粒释放其治疗有效载荷。吸入大的多孔胰岛素颗粒可使胰岛素的全身水平升高,并在96小时内抑制全身血糖水平,而小的无孔胰岛素颗粒仅在4小时内有此效果。通过吸入平均直径(20微米)约为传统吸入治疗颗粒10倍的多孔颗粒,也实现了睾酮的高全身生物利用度。