Liposome-loaded dissolvable microneedle patches for more efficient intradermal antigen delivery of Hepatitis B vaccine

Abstract

The aim of this study was to improve the efficacy of Hepatitis B surface antigen (HBsAg) vaccination via liposome-loaded dissolvable microneedle (Lipo-dMN) patches. HBsAg liposomes were prepared using the thin-film hydration method and subsequently incorporated into dissolvable microneedle patches via a pre-vacuum approach. Liposomes, dissolvable microneedle patches (dMN), and Lipo-dMN were characterized for encapsulation efficiency, mechanical properties, morphology, skin insertion, in vitro release, cellular uptake, and in vivo vaccination studies. The HBsAg was encapsulated into liposomes with encapsulation efficiencies around 50 %, particle size around 160 nm, and zeta potential around −20 mV. HBsAg can maintain its activity during the preparation of dMN and Lipo-dMN. The intact pyramid microneedle has a sharp end and strong mechanical properties that allow easy insertion into the ex vivo pig skin. The dMN and Lipo-dMN, with a mechanical property of 1.6 N, readily penetrate the epidermis and release the HBsAg and HBsAg liposome to modulate the immune response. A comprehensive comparison of HBsAg subcutaneous injection and intradermal delivery of HBsAg and HBsAg liposome by dMN revealed different levels of anti-HBsAg IgG antibody. Inoculation with dMN and Lipo-dMN resulted in significantly higher levels of anti-HBsAg IgG antibodies (p < 0.01) compared to subcutaneous injection of HBsAg. In addition, we found that IgG levels increased significantly (P < 0.05) with increased dose of subcutaneous injection of HBsAg and intradermal delivery of dMN, but the opposite effect was observed in Lipo-dMN. The possible mechanism for this observation may be the increased cellular uptake of liposomes by BMDCs upon long-term incubation. In summary, this study presents a promising approach to enhance HBsAg vaccination efficacy through the synergistic combination of liposomes and dissolvable microneedles at reduced vaccine doses.