Specific delivery of an immunosuppressive drug to splenic B cells by antigen-modified liposomes and its antiallergic effect

Abstract

Background: Use of the reverse targeting drug delivery system (RT-DDS) is a new targeting strategy based on the specific delivery of drugs to immune cells in antigen-sensitized animals by using antigen-modified liposomes, and it is expected to be a curative treatment for allergic diseases.Purpose: Herein, we prepared ovalbumin (OVA)-modified liposomes encapsulating the immunosuppressive drug FK506 (OVA-LipFK) and aimed to demonstrate the delivery selectivity of the liposomes to splenic B cells, and its antiallergic effect in an OVA-sensitized allergic model mouse.Methods: Fluorescently labeled OVA-LipFK was intravenously injected into OVA-sensitized mice, and the intrasplenic localization of liposomes was observed. The antiallergic effect of OVA-LipFK in OVA-sensitized mice was examined by measuring the blood levels of OVA-specific IgE and IgG antibodies.Results and discussion: OVA-LipFK was co-localized to not only B cells but also germinal centers, in the spleen of OVA-sensitized mice. However, there was no accumulation of unmodified liposomes encapsulating FK506 (LipFK) in the splenic B-cell area. In a therapeutic study, OVA-LipFK significantly suppressed the production of both OVA-specific IgE and IgG antibodies in OVA-sensitized mice after the animals had been boosted with OVA, whereas LipFK showed little antiallergic effect.Conclusions: The present study suggested that the introduction of RT-DDS for use with immunosuppressive drugs could be useful for the treatment of allergic diseases.