Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

Abstract

Background Transcutaneous vaccines have received wide attention due to their easy-to-use, needle-free, noninvasive delivery. However, the novel barrier function of stratum corneum hinders the transport of antigen and adjuvant in transcutaneous immunization. Novel nanoscale delivery systems employing, for example, liposomes and nanoparticles, have been widely investigated to overcome the penetration barrier of stratum corneum for effective transcutaneous immunization. Objective The objective of this study was to prepare two types of flexible liposomes and determine their efficacies for the transcutaneous delivery of antigen and the subsequent immune response induced in vivo. Methods Ovalbumin (OVA) liposome-based transcutaneous vaccines were prepared using reverse-phase evaporation and film-dispersion methods. Particle sizes and antigen encapsulating efficiency were then evaluated. After application to bare mouse skin, topical sites were examined for the presence of fluorescence-labeled liposome. The efficacy of the transcutaneously delivered OVA-loaded flexible liposome in activating the immune responses was investigated by detecting serum immunoglobulin G levels. The influence of an adjuvant, imiquimod, in the transcutaneous immunization was also tested. Results Two flexible liposomes with well-encapsulated OVA were successfully prepared by film-dispersion or reverse-phase evaporation methods. The sizes of the prepared flexible liposomes ranged from 200 to 400 nm. In vivo, the fluorescence-labeled liposome was detected in hair-follicle ducts, indicating that the flexible liposome can penetrate the skin barrier through the hair follicles. Upon transcutaneous administration, the OVA-encapsulated flexible liposome elicited a strong immune response similar to that of positive control (ie, OVA solution administrated by subcutaneous injection with Al(OH) 3 as an adjuvant). Co-administration of imiquimod with the OVA-loaded liposome expressed a significant enhancement on the transcutaneous immune responses. Conclusion Results of this study highlight the nanoscale formulation, flexible liposome, as a promising carrier for the transcutaneous delivery of antigen proteins. Imiquimod was shown to be an effective adjuvant as a transcutaneous immunization enhancer with the potential for transcutaneous vaccine development.

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

“…A 2-phased reaction of skin to barrier disruption has been described [39]. Some authors found a Th2- and eosinophil-focused response after tape stripping as well as increased IgG titters of anti-ovalbumin after application of a correspondent vaccine when applied on tape-stripped skin [38,40,41]. In this context different vaccine formulations might be worth comparing since other findings suggest higher antigen amount distribution to the hair follicle when the compound is encapsulated in nanoparticles [42].…”

Emerging Trends in Lipid-Based Vaccine Delivery: A Special Focus on Developmental Strategies, Fabrication Methods, and Applications

“…25 mg of the antigen was dissolved in distilled water and the resulting aqueous phase was used to hydrate the lipid film. Hydration of the lipid film resulted in the formation of vesicular structures entrapping the antigen in the aqueous core [ 85 ]. The film hydration method for liposome preparation is depicted in Figure 8 .…”

Drug Delivery with Topically Applied Nanoparticles: Science Fiction or Reality?

“…Moreover, research into particulate drug delivery systems via the skin is continuously growing [5,6,7]. Liposomes are already well known for their efficacy to increase drug delivery via the stratum corneum [8,9,10]. Although the mechanisms of liposome penetration and distribution of the active compounds were investigated in several studies [11,12,13], various mechanisms are still under discussion to explain the enhanced delivery of drugs from traditional liposomes.…”