Preparation and in vivo study of dry powder microspheres for nasal immunization

Abstract

The immunoadjuvant potential of alginate microspheres as delivery system, and cross-linked dextran microspheres (CDM) as absorption enhancer and excipient for powder of alginate microspheres, were evaluated. Alginate microspheres were prepared by emulsification method. Microspheres encapsulated with tetanus toxoid (TT) or Quillaja saponin (QS) were nasally administered to rabbits, three times in 2 weeks interval and serum IgG and nasal lavage sIgA titers were determined by ELISA. The mean diameter of microspheres was about 1.5 μm. Release of TT and QS was 13.1 ± 1.4% and 31.8 ± 4.3% after 4 h. The serum IgG titer induced with (TT)_ALG microspheres was higher than TT solution (P<0.001). Addition of QS or CDM adjuvant, in separate, to (TT)_ALG microspheres could not significantly increase the immune responses (P>0.05), but the highest systemic IgG titers induced with (TT+QS)_ALG+CDM (P<0.01). The sIgA titer induced with (TT)_ALG microspheres was higher than TT solution (P<0.05). The highest mucosal sIgA titers were seen in animals immunized with (TT)_ALG+CDM (P<0.05). Co-encapsulation of QS and TT in microspheres did not increase the sIgA titers. When CDM was added to alginate microspheres encapsulated with TT or TT+QS, the highest mucosal and systemic responses were observed.

Keywords::

• Nasal immunization
• alginate microspheres
• cross-linked dextran microspheres
• Quillaja saponins
• tetanus toxoid

Acknowledgements

This project was supported by a grant from Vice Chancellor for Research, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.

Declaration of interest

The authors report no conflict of interest.