Immunogenicity of diphtheria toxoid and poly(I:C) loaded cationic liposomes after hollow microneedle-mediated intradermal injection in mice

Int J Pharm. 2018 Aug 25;547(1-2):250-257. doi: 10.1016/j.ijpharm.2018.06.001. Epub 2018 Jun 2.


In this study, we aimed to investigate the immunogenicity of cationic liposomes loaded with diphtheria toxoid (DT) and poly(I:C) after hollow microneedle-mediated intradermal vaccination in mice. The following liposomal formulations were studied: DT loaded liposomes, a mixture of free DT and poly(I:C)-loaded liposomes, a mixture of DT-loaded liposomes and free poly(I:C), and liposomal formulations with DT and poly(I:C) either individually or co-encapsulated in the liposomes. Reference groups were DT solution adjuvanted with or without poly(I:C) (DT/poly(I:C)). The liposomal formulations were characterized in terms of particle size, zeta potential, loading and release of DT and poly(I:C). After intradermal injection of BALB/c mice with the formulations through a hollow microneedle, the immunogenicity was assessed by DT-specific ELISAs. All formulations induced similar total IgG and IgG1 titers. However, all the liposomal groups containing both DT and poly(I:C) showed enhanced IgG2a titers compared to DT/poly(I:C) solution, indicating that the immune response was skewed towards a Th1 direction. This enhancement was similar for all liposomal groups that contain both DT and poly(I:C) in the formulations. Our results reveal that a mixture of DT encapsulated liposomes and poly(I:C) encapsulated liposomes have a similar effect on the antibody responses as DT and poly(I:C) co-encapsulated liposomes. These findings may have implications for future design of liposomal vaccine delivery systems.

Keywords: Diphtheria toxoid; Hollow microneedle; Immunogenicity; Intradermal vaccination; Liposomes; Poly(I:C).

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibody Formation / immunology
  • Cations
  • Diphtheria Toxoid / administration & dosage*
  • Diphtheria Toxoid / immunology
  • Drug Delivery Systems
  • Drug Liberation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoglobulin G / immunology*
  • Injections, Intradermal
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Needles
  • Particle Size
  • Poly I-C / administration & dosage*
  • Poly I-C / immunology
  • Vaccination


  • Adjuvants, Immunologic
  • Cations
  • Diphtheria Toxoid
  • Immunoglobulin G
  • Liposomes
  • Poly I-C