Immunological responses to nasal delivery of free and encapsulated tetanus toxoid: studies on the effect of vehicle volume.
In light of growing interest in the intranasal route as a non-invasive mode of immunisation, we have investigated the relationship between the volume of liquid instilled into the nasal passages and the development of subsequent immunological responses. Groups of six mice were intranasally immunised with soluble or microsphere encapsulated tetanus toxoid on days 1, 14 and 28 of the experiment. Microsphere suspensions and tetanus toxoid solutions were nasally instilled in two different volumes of buffer (10 or 50 microl). Nasal instillation of microspheres in 10 microl of buffer generated statistically depressed (P<0.001) tertiary serum anti-toxoid IgG responses in comparison to animals immunised with 10 or 50 microl of soluble vaccine, or 50 microl of microsphere suspension. Relative to other treatments, nasal inoculation of encapsulated toxoid suspended in 50 microl generated statistically (P<0.05) superior levels of specific IgG and IgA antibodies in day 49 lung wash samples. When radiolabelled microspheres were nasally instilled into mouse nares in 50-microl volumes of buffer, a significant portion of the dose (48%) entered the lungs (P<0.001), whereas more particles remained in the nasal passages when a smaller (10 microl) volume of suspension was given (P<0.001). These biodistribution and immunological data indicate that to generate optimal bronchopulmonary and systemic responses in concert following nasal administration, microparticulated vaccines should be administered with a delivery device that targets the formulation to distal regions of the nasal passages and the lower respiratory tract.
Eyles
J E
JE
Pharmaceutical Sciences, Life and Health Sciences, Aston University, Birmingham, UK.
Williamson
E D
ED
Alpar
H O
HO
D000281:Administration, Intranasal; D000818:Animals; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D012996:Solutions; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D007074:Immunoglobulin G; D012996:Solutions; D013745:Tetanus Toxoid