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. 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.

A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin.

In a low inflammatory skin environment, Langerhans cells (LCs) - but not dermal dendritic cells (dDCs) - contribute to the pivotal process of tolerance induction. Thus LCs are a target for specific-tolerance therapies. LCs reside just below the stratum corneum, within the skin's viable epidermis. One way to precisely deliver immunotherapies to LCs while remaining minimally invasive is with a skin delivery device such as a microprojection arrays (MPA). Today's MPAs currently achieve rapid delivery (e.g. within minutes of application), but are focussed primarily at delivery of therapeutics to the dermis, deeper within the skin. Indeed, no MPA currently delivers specifically to the epidermal LCs of mouse skin. Without any convenient, pre-clinical device available, advancement of LC-targeted therapies has been limited. In this study, we designed and tested a novel MPA that delivers ovalbumin to the mouse epidermis (eMPA) while maintaining a low, local inflammatory response (as defined by low erythema after 24 h). In comparison to available dermal-targeted MPAs (dMPA), only eMPAs with larger projection tip surface areas achieved shallow epidermal penetration at a low application energy. The eMPA characterised here induced significantly less erythema after 24 h (p = 0.0004), less epidermal swelling after 72 h (p < 0.0001) and 52% less epidermal cell death than the dMPA. Despite these differences in skin inflammation, the eMPA and dMPA promoted similar levels of LC migration out of the skin. However, only the eMPA promoted LCs to migrate with a low MHC II expression and in the absence of dDC migration. Implementing this more mouse-appropriate and low-inflammatory eMPA device to deliver potential immunotherapeutics could improve the practicality and cell-specific targeting of such therapeutics in the pre-clinical stage. Leading to more opportunities for LC-targeted therapeutics such as for allergy immunotherapy and asthma.