Effect of Dimethyl-β-Cyclodextrin Concentrations on the Pulmonary Delivery of Recombinant Human Growth Hormone Dry Powder in Rats
Effect of Dimethyl-β-Cyclodextrin Concentrations on the Pulmonary Delivery of Recombinant Human Growth Hormone Dry Powder in Rats
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DOI：
10.1002/jps.21353
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发表时间：
2008-12-01
影响因子：
3.8
通讯作者：
Tajerzadeh, Hosnieh
中科院分区：
文献类型：
--
作者：
Jalalipour, Monireh;Najafabadi, Adolhossien Rouholamini;Tajerzadeh, Hosnieh
本文的目的是制备和表征重组人生长激素（rhGH）的可吸入干粉，并评估其对大鼠全身递送蛋白质的功效。通过在初始进料中使用不同摩尔比的二甲基-β-环糊精（DM β CD）进行喷雾干燥来制备粉末。进行尺寸排阻色谱以确定DM β CD对喷雾干燥期间rhGH聚集的保护作用。通过增加DM β CD的浓度，rhGH聚集从9.67%（不存在DM β CD）降低至0.84%（在喷雾溶液中以1000摩尔比使用DM β CD）。喷雾干燥（SD）粉末的气溶胶性能使用Andersen级联撞击器进行评价。分别以10、1.00和1000摩尔比使用DM β CD获得53.49%、33.40%和23.23%的细颗粒分数值。体内研究显示，在大鼠中，含10、100和1000摩尔比的DM β CD溶液喷雾干燥后产生的粉末经气管内吹入后的绝对生物利用度分别为25.38%、76.52%和63.97%。总之，考虑到SD粉末的蛋白质聚集和气雾剂性能以及通过大鼠肺给药后的全身吸收，获得了适当的环糊精浓度。(c)2008 Wiley-Liss，Inc.和美国药学协会药物科学杂志97：5176-5185，2008
The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl-beta-cyclodextrin (DM beta CD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DM beta CD on the rhGH aggregation during spray drying. By increasing the concentration of DM beta CD, rhGH aggregation was decreased from 9.67 (in the absence of DM beta CD) to 0.84% (using DM beta CD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DM beta CD at 10, 1.00, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DM beta CD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5176-5185, 2008