muramidase and octanoic-acid

Transcutaneous immunization (TCI) is a novel vaccination strategy, which is expected to have therapeutic applications. However, to develop effective TCI systems, a simple, non-invasive and safe transdermal formulation is required. This study developed a novel TCI system utilizing the co-administration of a liposoluble absorption enhancer, propylene glycol monocaprylate (PGMC) and hydrosoluble protein antigen without pretreatment of any typical adjuvants and disruption of the skin. Novel transdermal formulations were also prepared with sodium salicylate (NaSal) as a hydrotropic agent to improve the solubility of poorly water-soluble substances.. The TCI system, which used a transdermal formulation containing hen lysozyme (HEL) and PGMC, solubilized with NaSal, resulted in a substantial HEL-specific antibody response in an HEL dose-dependent manner even in the absence of potent adjuvants, such as cholera toxin (CT). We also investigated whether NaSal activates antigen-presenting cells in vitro to clarify the mechanisms of antibody production by the hydrotropic formulation. NaSal enhanced the expression of MHC class II molecules and increased the production of IL-12 and TNF-α in dendritic cells, which were stimulated by lipopolysaccharide in vitro, indicating that NaSal had an effective adjuvant-like property. Moreover, the use of NaSal in the TCI system did not induce an HEL-specific, IgE-dependent anaphylactic reaction.. Our TCI system using a hydrotropic formulation effectively and safely induced the intended immune response, and this system thus represents a new advantageous method that will result in improved TCI strategies.

Topics: Administration, Cutaneous; Animals; Antibodies; Antigens; Caprylates; Cells, Cultured; Cytokines; Dendritic Cells; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluorescein-5-isothiocyanate; Histocompatibility Antigens Class II; Hydrophobic and Hydrophilic Interactions; Immunization; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Muramidase; Propylene Glycol; Skin; Sodium Salicylate; Solubility