Microneedle-based two-step transdermal delivery of Langerhans cell-targeting immunoliposomes induces a Th1-biased immune response

Novel Coronavirus is affecting human’s life globally and vaccines are one of the most effective ways to combat the epidemic. Transcutaneous immunization based on microneedle (MN) has attracted much attention because of its painlessness, rapidity, high efficiency and good compliance. In this study, CD11c monoclonal antibody-immunoliposomes (OVA@CD11c-ILP) actively targeting to Langerhans cells (LCs) were successfully prepared and were delivered by the microchannels of skin produced by MN to induce an immune response in vivo. OVA@CD11c-ILP could be targeted to LCs by conjugating CD11c monoclonal antibody to the surface of the ILP. OVA@CD11c-ILP promoted the maturation of dendritic cells (DCs) and the uptake and endocytosis of antigen by LCs.

Highlights

• Immunoliposomes can actively target Langerhans cells and effectively promote the
presentation of antigens.

• Immunoliposomes can reach the draining lymph nodes and spleen by microneedle.

• Immune response stimulated by immunoliposomes combined with microneedle was Th1-biased.

Moreover, OVA@CD11c-ILP immunization can significantly inhibit tumor growth and prolong overall survival. Furthermore, a higher antibody’s titer ratio of IgG1/IgG2a indicated that the immune response stimulated by this immunization method was Th1-biased and the liposomes showed Th1-type adjuvant effect. In conclusion, the combination delivery system of immunoliposomes and microneedle can significantly improve the efficiency of antigen presentation and effectively activate cellular immune responses in the body, which is expected to be a promising transdermal immune strategy.

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Materials:

1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine [methoxy (polyethylene glycol) −2000] (mPEG2000-DSPE) and egg phosphatidylcholine (EPC-3) were purchased from Lipoid company (Germany). 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine [Malermide methoxy (polyethylene glycol)-2000] (Mal-PEG2000-DSPE) was obtained from Creative company (USA). Ovalbumin (OVA), cholesterol (CHO), 2-Iminothiolane hydrochloride (2-IT) and cholera toxin (CT) were purchased from Sigma (USA). Fluorescence-labeled rat anti-mouse monoclonal CD40, CD80, CD86, CD11c antibody and Goat anti-mouse monoclonal IgG-HRP, IgG1-HRP, IgG2a-HRP, IgA-HRP antibody were purchased from eBioscience (USA) and Santa Cruz (USA) respectively. The materials used in cell experiment were obtained from Gibco (USA). Mouse Th1/Th2/Th17 Cytokine Kit was purchased from BD company (USA). EL4 cells and E.G7-OVA cells were kindly gift from the National Key Laboratory of Medical Immunology (Shanghai, People’s Republic of China). Microneedle was donated by Dr. Hua Lin from Nanjing University.

Yingjie Yu, Huan Wang, Beibei Guo, Bingkai Wang, Zhan Wan, Yunchang Zhang, Linhong Sun, Feng Yang,
Microneedle-based two-step transdermal delivery of Langerhans cell-targeting immunoliposomes induces a Th1-biased immune response,
European Journal of Pharmaceutics and Biopharmaceutics, Volume 177, 2022, Pages 68-80, ISSN 0939-6411,
https://doi.org/10.1016/j.ejpb.2022.06.004.