Evaluation of garlic and small onion derived nanovesicle topical formulation for the treatment of inflammatory skin disease, Psoriasis.

Exosomes are a sub-set of extracellular vesicles, actively secreted from mammalian cells. Since its discovery, exosomes have received considerable attention in both therapeutic avenue and also as nanocarrier for biological cargo. Recent reports have highlighted the presence of similar nanosized vesicles in edible plants which are currently known as exosome-like nanoparticle/vesicles (ENVs). These ENVs are loaded with plant derived microRNAs, protein, lipids and bioactive compounds. The discovery of these ENVs may offer alternate solutions for longlasting problems in the field of plant bioactives, especially on their bioavailability. Psoriasis is an auto immune disease of skin, causing significant morbidity to patients, with corticosteroids as the only treatment option. Psoriasis is characterized by uncontrolled inflammation and incomplete differentiation of keratinocytes. Since, both epidermal hyperplasia and intra-dermal inflammation causes psoriasis pathogenesis, perfect anti-psoriatic formulation needs to penetrate the epidermis and reach the dermal compartment to target inflammatory cells. ENVs have never been investigated for treatment of Psoriasis. In this work, we screened a panel of edible plant ENVs for their ability to promote spontaneous differentiation in human keratinocytes. In this screen, ENVs derived from small onion and garlic pods promote differentiation of human keratinocytes but also exhibit anti-inflammatory activity in vitro suggesting that ENVs could be used to curb inflammation and restore barrier function in Psoriatic epidermis. To test this, both onion and garlic ENVs were formulated as a hydrogel. Topical application of both onion and garlic ENVs in mice with psoriatic like skin inflammation (induced by imiquimod) led to complete recovery of normal skin phenotype evidenced by reduction in epidermal hyperplasia and suppression of inflammatory cytokines in vivo. To understand the mechanism behind the anti-inflammatory activity of garlic and onion ENVs on Psoriasis, we profiled the global transcriptome of garlic and onion ENV treated HaCaT keratinocytes by next generation sequencing. Mango ginger ENVs were used as an added control. Our results indicate that both garlic and onion ENVs primarily function via the suppression of IL17 pathway, a key driver cytokine involved in psoriasis pathogenesis, highlighting its therapeutic potential.