Development of Phospholipids Vesicular Nanocarrier for Topical Delivery of Tea Tree Oil in Management of Atopic Dermatitis Using BALB/c Mice Model

Abstract

This work aims to develop and evaluate the efficacy of tea tree oil (TTO) ethosomal cream with improved deposition in skin layers for treatment of atopic dermatitis (AD). Ethosomes of TTO are developed using phosphatidylcholine (2% and 3% w/v) and ethanol (20%, 30%, and 40% w/v). Ethosomes are evaluated for percent entrapment efficiency (%EE), vesicle size, zeta potential, and in vitro drug diffusion. Ethosomal creams with optimized ethosomal dispersion are developed and evaluated for physicochemical parameters, thermal stability, ex vivo permeation, skin retention, and in vitro cytotoxicity using HaCat skin cell lines in comparison to conventional creams of TTO. In vivo investigations of optimized creams are performed using BALB/c mice model. The %EE, vesicle size, and zeta potential for optimized ethosomes are found to be 76.19 ± 3.26%, 333.6 nm, and -35.3 mV, respectively. Ethosomal creams showed higher deposition in the epidermis and dermis. The optimized creams are non-cytotoxic to HaCat cell lines. The creams significantly reduce the inflammatory response by decreasing the clinical score and infiltration of white blood cells, eosinophils, and IgE antibodies. Overall efficacy of ethosomal cream is higher than conventional cream. In conclusion, optimized ethosomal cream of TTO shows good efficacy for treatment of AD. Practical applications: The method used for the formulation of ethosomes is simple and can be easily scaled up on the industrial level. The loading of TTO within ethosomes can increase the efficiency by enhanced drug deposition in the epidermis and might also improve its stability against oxidative degradation. Topical ethosomal cream of TTO can improve patient compliance by avoidance of adverse effects linked with corticosteroids and could be a possible complementary or alternative therapy in management of AD.

Emerging topical drug delivery approaches for the treatment of Atopic dermatitis

“…The cream retained at greater extent in epidermis and dermis, decreased the clinical scores and inflammatory responses. It showed no cytotoxic effect on HaCat cell lines 62 …”

AKVANO®: A Novel Lipid Formulation System for Topical Drug Delivery—In Vitro Studies

“…However, since the hydrodynamic radius is generally larger than the actual physical radius (due to solvation effects), it can be stated that the data measured for all formulations are probably on the small side for micelles, and especially for the DMPC formulation exhibiting data much smaller than what would be expected for micelles. In contrast, according to the literature, in phospholipid/ethanol systems with higher content of water, vesicular systems are formed with much larger aggregate size (ranging from one to several orders of magnitude larger) [17,18].…”

New Insights in Topical Drug Delivery for Skin Disorders: From a Nanotechnological Perspective

“…From the findings, it was observed that the prepared ethosomal cream deposited more in skin layers, was safe during cell line examination, and efficiently minimized inflammation through IgE antibodies, WBC, eosinophils infiltration, and a decreased clinical score as compared to a simple TTO cream. Hence, it has been approved as more efficacious for AD treatment . Three vesicular cyanocobalamin-loaded formulations, i.e., ethosomes, liposomes, and transferosomes, through a film-hydration technique were prepared with better permeation efficiency across skin layers for the scavenging activity against nitric oxide in pathological conditions of AD and psoriasis.…”