Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination

• Published in: European journal of pharmaceutical sciences 2015-12, Vol.80, p.16-25
• Main Authors: Li, Hui-Shan, Singh, Bijay, Park, Tae-Eun, Hong, Zhong-Shan, Kang, Sang-Kee, Cho, Chong-Su, Choi, Yun-Jaie
• Format: Article
• Language: English
• Subjects: Adjuvant; Administration, Intranasal; Animals; Antigen presenting cells (APCs); Antigen-Presenting Cells - immunology; Cell Line; Female; Immunoglobulin A, Secretory - blood; Immunoglobulin A, Secretory - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Mannan; Mannans - administration & dosage; Mannose receptor targeting; Mice; Mice, Inbred BALB C; Microspheres; Mucoadhesive microspheres; Nasal vaccine; Polymethacrylic Acids - administration & dosage; Receptors, Mitogen - immunology; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2015.09.014

Mucosal vaccination of protein as an antigen requires appropriate delivery or adjuvant systems to deliver antigen to mucosal immune cells efficiently and generate valid immune responses. For successful nasal immunization, the obstacles imposed by the normal process of mucociliary clearance which limits residence time of applied antigens and low antigen delivery to antigen presenting cells (APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain efficient immune responses. The potential adjuvant ability of Man-TEM for intranasal immunization was confirmed by in vitro and in vivo experiments. In mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and mucosal sIgA than the soluble OVA group due to the specific recognition of MR of APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit systemic and mucosal immunity. [Display omitted]