Application of RPMI 2650 nasal cell model to a 3D printed apparatus for the testing of drug deposition and permeation of nasal products

被引:54
作者
Pozzoli, Michele [1 ]
Ong, Hui Xin [2 ,3 ]
Morgan, Lucy [4 ]
Sukkar, Maria [1 ]
Traini, Daniela [2 ,3 ]
Young, Paul M. [2 ,3 ]
Sonvico, Fabio [1 ,5 ]
机构
[1] Univ Technol Sydney, Grad Sch Hlth Pharm, 15 Broadway, Ultimo, NSW 2007, Australia
[2] Univ Sydney, Sydney Med Sch, Woolcock Inst Med Res, Resp Technol, 431 Glebe Point Rd, Glebe, NSW 2037, Australia
[3] Univ Sydney, Sydney Med Sch, Discipline Pharmacol, 431 Glebe Point Rd, Glebe, NSW 2037, Australia
[4] Univ Sydney, Sydney Med Sch, Concord Clin Sch, Concord Repatriat Gen Hosp, Sydney, NSW, Australia
[5] Univ Parma, Dept Pharm, 27A Parco Area Sci, I-43124 Parma, Italy
基金
澳大利亚研究理事会;
关键词
RPMI; 2650; Transporter expression; Nasal permeation; Mucus; Air Liquid Interface; Primary nasal cell; 3D printing; Deposition; Dissolution; Permeation; IN-VITRO MODEL; INTRANASAL CORTICOSTEROIDS; P-GLYCOPROTEIN; DELIVERY; TRANSPORT; OPPORTUNITIES; OPTIMIZATION; BUDESONIDE; MODULATION; CHALLENGES;
D O I
10.1016/j.ejpb.2016.07.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to incorporate an optimized RPMI2650 nasal cell model into a 3D printed model of the nose to test deposition and permeation of drugs intended for use in the nose. The nasal cell model was optimized for barrier properties in terms of permeation marker and mucus production. RT-qPCR was used to determine the xenobiotic transporter gene expression of RPMI 2650 cells in comparison with primary nasal cells. After 14 days in culture, the cells were shown to produce mucus, and to express TEER (define) values and sodium fluorescein permeability consistent with values reported for excised human nasal mucosa. In addition, good correlation was found between RPMI 2650 and primary nasal cell transporter expression values. The purpose-built 3D printed model of the nose takes the form of an expansion chamber with inserts for cells and an orifice for insertion of a spray drug delivery device. This model was validated against the FDA glass chamber with cascade impactors that is currently approved for studies of nasal products. No differences were found between the two apparatus. The apparatus including the nasal cell model was used to test a commercial nasal product containing budesonide (Rhinocort, AstraZeneca, Australia). Drug deposition and transport studies on RPMI 2650 were successfully performed. The new 3D printed apparatus that incorporates cells can be used as valid in vitro model to test nasal products in conditions that mimic the delivery from nasal devices in real life conditions. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:223 / 233
页数:11
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