Background: Dermal/skin disorders (inflammation, infection, and cancer) globally affect people of all ages, sexes, lifestyles and drastically reduces the quality of life along with decreased life expectancy.  Unfortunately, billions of dollars and valuable patients’ time are spent on its prevention, cure, and care.  There are several oral, parenteral, or topical formulations/dosage forms used for treating various skin pathologies. Due to decreased bioavailability, pharmaceutically inelegant, adverse effects, and hypersensitivity-related complications, new novel skin formulations are currently being investigated. At present, various natural products are high in demand due to the beneficial bioactives that exhibit multipotent pharmacodynamics effects with no/minimal contraindications.  Thuja occidentalis contain essential oils, coumarins, and flavonoids.  They exhibited antioxidant, anti-inflammatory, anticarcinogenic, antibiotic, and trophic actions which renders it to be used for preventing and treating various pathologies in humans.  However, Thuja occidentalis has several concerns associated with its oral routes. The bioactives present in the Thuja occidentalis (Thujone, Quercetin) has high irritation potential because it erodes the mucous membrane, produce significant tissue damage, irritation, and ulceration.  Therefore, a novel colloidal drug delivery system is required to potentially carry out multiple tasks in a predefined sequence to deliver the bioactives of Thuja occidentalis effectively.   Subsequently, topical routes would be more therapeutically beneficial due to reduced risk of systemic adverse effects with decreased possibility of drug interactions. Phytosomes, are an innovative drug delivery system for current and future global health care. This novel phytosomal drug delivery system holds great promise for reaching the goal of controlled as well as site-specific drug release from the vesicles across the biological membrane with minimal/no irritation, and ulceration.

Aim: In the current study, novel phytosomal formulations with the Thuja occidentalis extract were formulated and additionally evaluated for their morphology, stability, spreadability, in vitro release (Quercetin), and in vivo skin hypersensitivity reactions.

Results: Novel phytosomal formulations of Thuja occidentalis were stable, exhibited high bioavailability, and more prominently had no in vivo allergic manifestations(no hypersensitivity reactions or did not induce skin irritation). Moreover, the oral Quercetin bioavailability is very poor (0.001% - 0.01%) and is furthermore significantly affected by a high level of intersubject variability.  Thus, valid phytosomal formulations of Thuja occidentalis can be a suitable cosmetic and pharmaceutical dosage form for preventing and therapeutically treating various skin diseases/disorders.