Immunological responses to nasal delivery of free and encapsulated tetanus toroid: 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 sir mice were intranasally immunised with soluble or microsphere encapsulated tetanus toroid on days 1, 14 and 28 of the experiment. Microsphere suspensions and tetanus toroid solutions were nasally instilled in two different Volumes of buffer (10 or 50 mu l). Nasal instillation of microspheres in 10 mu l of buffer generated statistically depressed (P <0.001) tertiary serum anti-toroid IgG responses in comparison to animals immunised with 10 or 50 mu l of soluble vaccine, or 50 mu l of microsphere suspension. Relative to other treatments, nasal inoculation of encapsulated toroid suspended in 50 mu l 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-mu l 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 mu l) 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. (C) 1999 Elsevier Science B.V. All rights reserved.