A preliminary investigation on hydrogel disks imbibed with enriched transfersomes as promising tool to promote the cutaneous deposition of vaccine antigens

The skin is an appealing and easily accessible route of administration for fast mass vaccination. However, it relies mainly on injection, meaning no immunization is achieved locally. In addition, pain, fear, and injuries strongly affect and reduce the effectiveness and adherence of patients to vaccination plans. Non-invasive routes of administration offer a safe and reliable solution. On these bases, three series of phospholipid vesicles were eco-friendly developed and adequately modified to pursue cutaneous immunization. Ovalbumin was selected as the model antigen, whereas transfersomes were chosen over liposomes because of their higher capability to cross the skin. Glycerol, sodium hyaluronate, or their combination were added to further improve their penetration, and this led to small (< 60 nm), homogenous vesicles (polydispersity index < 0.2), stable for up to 9 months. The colloidal formulations, alone or combined with occlusive strategies (achieved by cling film or hydrogel disks), were tested on tape-stripped skin to facilitate their application in a potential real-life context. While the enriched transfersomes alone provided better ovalbumin accumulation into the skin, the combination with cling film and especially with the hydrogel disks boosted their performance even further (using the hydrogel disks, in the epidermis, the ovalbumin accumulated ranged from ∼30 to ∼40 μg/cm 2 and in the dermis from ∼4 to ∼10 μg/cm 2 ). Despite the antigen-presenting assay do not show any immunogenicity for these vesicles (p > 0.05 with respect to the ovalbumin solution tested at the same dose), they are expected to perform better than the ovalbumin solution due to the protection and the enhanced skin deposition they provide. In addition, all the formulations can be safely administered as they are highly biocompatible in a wide range of doses (> 100% from 0.05 to 50 μg/mL of ovalbumin) and do not exert any inflammatory response. However, further studies are needed to confirm these promising preliminary results.