Quality-by-Design Guided Development and Evaluation of Tea Tree Oil-Based Tacrolimus-Loaded Nanostructured Carrier Gel for Psoriasis Therapy

Abstract

Psoriasis is a chronic skin disease primarily caused by inflammation, resulting in abnormal growth of epidermal cells that cause skin reddening, scaling, and irritation. Tacrolimus (TAC), a poorly soluble immunosuppressant drug, was used in the current study for the management of psoriasis. Moreover, tea tree oil (TTO) was also utilized as a functional excipient to synergize the efficiency of the drug. Here, nanostructured lipidic carriers (NLCs) were formulated using a high-shear homogenization method. To ensure a robust and scientifically optimized formulation, a Quality by Design (QbD) approach was implemented to systematically investigate the influence of formulation variables on critical quality attributes and to obtain an optimized nanoformulation. The developed nanocarriers showed 108.65 ±2.4 nm particle size, 0.265±0.028 polydispersity index, and ∼23.9 mV zeta potential. Morphological examination revealed the spherical structure of nanoformulations with uniform distribution. Differential scanning colorimeter studies showed the absence of a crystalline state of the drug, when incorporated in the formulation. Furthermore, gel formulations of drug-embedded NLCs were characterized for pH, viscosity, and spreadability. In vivo model was used to elucidate the higher efficacy of the developed formulation. In this work, different studies highlight the potential of tacrolimus loaded novel gel including the complementary advantages of tea tree oil.