Development and in vivo evaluation of a novel semi-solid nanostructured lipid carrier of fluticasone propionate for the treatment of atopic dermatitis using a quality by design approach

Abstract

Atopic Dermatitis (AD) is a chronic inflammatory skin condition that significantly affects patients’ quality of life. This study focuses on the development of an innovative semi-solid nanostructured lipid carrier (NLC) dispersion containing fluticasone propionate (FP), aimed at enhancing therapeutic efficacy in the treatment of AD while minimising the systemic side effects associated with corticosteroids. The semi-solid NLC dispersions were prepared using a novel single-step preparation method. This method allows the formulations to maintain a colloidal particle size despite their high lipid content and semi-solid consistency. Particle size and drug release rate were identified as critical attributes, and Quality by Design (QbD)-assisted optimisation was carried out using computer-based modelling. The optimum formulation had an average particle size of 187.6 ± 4.613 nm, which was within the targeted range. The polydispersitiy index (PDI) value of 0.229 ± 0.019 indicates a relatively narrow size distribution. Furthermore, the amount of FP released from the optimum formulation at 24 h was 11.26 ± 0.14 %, the highest among all the semi-solid NLCs prepared in the study. Results from the skin bleaching assay, paw oedema test, transepidermal water loss (TEWL) measurement, and histopathological evaluation in rats with induced chronic atopic dermatitis demonstrated both the enhanced therapeutic potential, and the favourable safety profile of the optimum formulation compared to conventional formulations. These findings suggest that semi-solid NLCs may serve as a promising alternative for the effective topical treatment of atopic dermatitis and other skin diseases.