Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery

被引:16
作者
Bi, Ru [1 ]
Shao, Wei [1 ]
Wang, Qun [2 ]
Zhang, Na [1 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, Pharmaceut Coll, Jinan 250100, Shandong, Peoples R China
[2] Univ Kansas, Dept Chem & Petr Engn, Lawrence, KS 66045 USA
基金
中国国家自然科学基金;
关键词
Insulin (Ins); liposomes; dry powder inhalation (DPI); spray freeze drying (SFD); pulmonary delivery; intratracheal instillation;
D O I
10.1080/10611860802201134
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Nowadays, growing attention has been paid to the pulmonary region as a target for the delivery of peptide and protein drugs, especially macromolecules with systemic effect like insulin, since the pulmonary route exhibits numerous benefits to be an alternative for repeated injection. Furthermore, encapsulation of insulin into liposomal carriers is an attractive way to increase drug retention time and control the drug release in the lung; however, its long-term stability during storage in the reservoir and the process of aerosolization might be suspected when practically applied. Thus, the aim of this study was to design and characterize dry powder inhalation of insulin-loaded liposomes prepared by novel spray-freeze-drying method for enhanced pulmonary delivery. Process variables such as compressed air pressure, pump speed, and concentration were optimized for parameters such as mean particle diameter, moisture content, and fine particle fraction of the produced powders. Influence of different kinds and amounts of lyoprotectants was also evaluated for the best preservation of the drug entrapped in the liposome bilayers after the dehydration-rehydration cycle. The in vivo study of intratracheal instillation of insulin-loaded liposomes to diabetic rats showed successful hypoglycemic effect with low blood glucose level and long-lasting period and a relative pharmacological bioavailability as high as 38.38% in the group of 8IU/kg dosage.
引用
收藏
页码:639 / 648
页数:10
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