Non-invasive pulmonary aerosol delivery in mice by the endotracheal route

被引:177
作者
Bivas-Benita, M [1 ]
Zwier, R [1 ]
Junginger, HE [1 ]
Borchard, G [1 ]
机构
[1] Leiden Amsterdam Ctr Drug Res, Div Pharmaceut Technol, NL-2300 RA Leiden, Netherlands
关键词
pulmonary delivery; nanoparticles; aerosol application; mice; endotracheal administration;
D O I
10.1016/j.ejpb.2005.04.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In this report we present in detail a non-invasive pulmonary application method that can be a useful tool in studying drug and vaccine delivery to the lower airways. In this method the formulation is sprayed directly into the lungs of mice via the endotracheal route using a MicroSprayer (TM) aerolizer. Mean droplet size produced was 8 mu m, appropriate for deposition in the large airways. Endotracheal application of suspension of fluorescent nanospheres, 200 nm in size, by this method resulted in nanoparticle deposition in the smaller airways (bronchi and bronchioles). Mice showed full recovery one day after administration of 50 mu l of formulation. Furthermore, no mortality was observed as a result of the technique. We conclude that this endotracheal application is a useful tool for studying pulmonary drug delivery in mice. The technique is especially useful for the pulmonary application of vaccines, since it enables multiple administrations without a need for analgesics. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:214 / 218
页数:5
相关论文
共 18 条
[1]  
BECK SE, 1999, PED PULM S, P228
[2]   Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis [J].
Bivas-Benita, M ;
van Meijgaarden, KE ;
Franken, KLMC ;
Junginger, HE ;
Borchard, G ;
Ottenhoff, THM ;
Geluk, A .
VACCINE, 2004, 22 (13-14) :1609-1615
[3]   A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice [J].
Brown, RH ;
Walters, DM ;
Greenberg, RS ;
Mitzner, W .
JOURNAL OF APPLIED PHYSIOLOGY, 1999, 87 (06) :2362-2365
[4]  
CENTURY TJ, 2000, RESP DRUG DELIV, V7, P1
[5]   Airway delivery of cationic lipid: DNA complexes for cystic fibrosis [J].
Cheng, SH ;
Scheule, RK .
ADVANCED DRUG DELIVERY REVIEWS, 1998, 30 (1-3) :173-184
[6]   Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: Uses and limitations [J].
Driscoll, KE ;
Costa, DL ;
Hatch, G ;
Henderson, R ;
Oberdorster, G ;
Salem, H ;
Schlesinger, RB .
TOXICOLOGICAL SCIENCES, 2000, 55 (01) :24-35
[7]   Analysis of local and systemic immunological responses after intra-tracheal, intra-nasal and intra-muscular administration of microsphere co-encapsulated Yersinia pestis sub-unit vaccines [J].
Eyles, JE ;
Spiers, ID ;
Williamson, ED ;
Alpar, HO .
VACCINE, 1998, 16 (20) :2000-2009
[8]   Protection studies following bronchopulmonary and intramuscular immunisation with Yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres:: a comparison of efficacy [J].
Eyles, JE ;
Williamson, ED ;
Spiers, ID ;
Alpar, HO .
VACCINE, 2000, 18 (28) :3266-3271
[9]   Aerosol delivery of PEI-p53 complexes inhibits B16-F10 lung metastases through regulation of angiogenesis [J].
Gautam, A ;
Densmore, CL ;
Melton, S ;
Golunski, E ;
Waldrep, JC .
CANCER GENE THERAPY, 2002, 9 (01) :28-36
[10]   Mucosal antigen primes diabetogenic cytotoxic T-Lymphocytes regardless of dose or delivery route [J].
Hänninen, A ;
Braakhuis, A ;
Heath, WR ;
Harrison, LC .
DIABETES, 2001, 50 (04) :771-775