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.

Keywords:

• Allergy
• B cell
• germinal center
• FK506
• liposome
• OVA
• RT-DDS

Acknowledgements

We thank Astellas Pharmaceutical Co. Ltd. for the gift of FK506. We also thank Dr. Hiroaki Kanazawa at the Department of Anatomy, School of Nursing, University of Shizuoka, for valuable suggestions about the analysis of immune system histology.

We are very happy to know that Dr. Pieter Cullis will be awarded the Journal’s Life-time Achievement Award for 2016 of the Journal of Drug Targeting. Pieter is one of the outstanding researchers in the field of DDS, especially liposomal DDS. Naoto has always enjoyed discussing the liposome research with him during Liposome Research Days Conference, and other DDS meetings. Pieter came to Shizuoka, Japan in 1997 and gave us an exciting lecture at the Shizuoka DDS Conference. He visited Shizuoka again in 2012, and at that time he accepted Kosuke’s three-month stay in his laboratory as a visiting scientist. We wish him every success in his research.

Disclosure statement

The authors declare no conflict of interest.

Funding information

This work was supported by JSPS KAKENHI Grant Numbers 20390014, 24790047.