Development of a phototriggerable liposomal delivery system for emblica fruit extract for the treatment of psoriasis

Psoriasis is defined as an organ-specific autoimmune disease that causes red, itchy, and scaly plaques on skinsurfaces, leading to physical discomfort and a feeling of social embarrassment. Standard treatments of psoriasis includetopical administration of corticosteroids or anthralin and systemic treatment using methotrexate or acitretin. Despite the high therapeutic efficacy, these treatments have deleterious side effects. For example, prolonged exposure to corticosteroids may lead to steroid atrophy, rebound phenomenon, and addiction, while the use of methotrexate may cause myelosuppression, nephropathy, and fatigue. Recently, treatment using monoclonal antibodies has attracted muchattention due to its effectiveness but is limited due to the high treatment cost and frequency of antibody administration. As a result, there has been an interest in exploring an alternative treatment option for psoriasis using herbal and plant extracts that are relatively safe and affordable. Many herbal and plant extracts have been shown to possess antipsoriatic properties in previous studies.

The extract from Phyllanthus emblica fruit, abundant in Thailand, contains many active compounds, including gallic acid, cinnamic acid, 5-hydroxymethylfurfural, ellagic acid, β-daucosterol, and quercetin, which are responsible for its anti-inflammatory, antioxidant, antimicrobial and anti-fungal properties. More importantly, its therapeutic efficacytoward psoriasis, proven in a clinical study based on the modified psoriasis area and severity index (mPASI), wascomparable to that of corticosteroid treatment. However, Phyllanthus emblica extract in the topical formulation exhibited lower bioavailability, leading to less therapeutic efficacy.

To overcome this limitation, a liposomal delivery system is suggested. Liposomes are biocompatible, biodegradable, and capable of functionalization. Hydrophilic and hydrophobic compounds can be incorporated into the aqueous core and the hydrophobic tail matrix of liposomes, respectively. An increase in the bioavailability of liposome-encapsulated drugs is a result of the similarity of the liposomal bilayer to the biological membrane, allowing membrane fusion. Our research group has successfully formulated soybean-phosphatide-based liposomes with photosensitizing moieties that allow for a phototriggerable release of the drug content. Our results showed that the new liposomal delivery system incorporated with a photosentizer was able to increase the loading efficiencies and cellular uptake of the encapsulated active agents, leading to higher bioavailability.

Based on the reasons mentioned above, we propose the use of our liposomal delivery system incorporated with a photosentizer to deliver Phyllanthus emblica fruit extract for the treatment of psoriasis. The interferon-γ-induced human keratinocyte cell line (HaCaT) will be used as an in vitro model of psoriasis owing to the presence of an inflammatory autoimmune loop associated with human psoriasis. The outcome of this project is the potential therapeutic efficacy of Phyllanthus emblica fruit extract in a liposomal formulation to treat psoriasis. This formulation will be further assessed using preclinical and clinical studies.