Design, optimization, and evaluation of ferulic acid-loaded cubosomal cream for enhanced topical delivery and anti-hyperpigmentation efficacy.

OBJECTIVE: The goal of this study was to create and optimize a topical cream based on cubosomes for improved dermal delivery and stability of ferulic acid, a strong antioxidant with anti-hyperpigmentation properties that is limited by low photostability and skin permeability.

SIGNIFICANCE: Improving the stability of ferulic acid and regulating its skin distribution is crucial for its successful application in cosmeceutical formulations. Cubosomal nanocarriers offer a viable way to enhance photostability, solubility, and sustained release, improving therapeutic efficacy while preserving skin safety.

METHODS: Glyceryl monooleate and Poloxamer 407 were used to create ferulic acid-loaded cubosomes. The effects of almond oil and Sepineo P600 on viscosity and drug content were assessed using the Box-Behnken design to optimize cream formulation. Particle size analysis, entrapment efficiency, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rheological investigations were all part of the characterization. To clarify release mechanisms, kinetic models were fitted to in vitro release data. Tyrosinase inhibition studies evaluated the effectiveness of anti-hyperpigmentation, while MTT and RT-PCR assays were used to assess biocompatibility.

RESULTS: The optimized formulation developed nanosized particles with thixotropic flow behavior, skin-compatible pH, and high entrapment efficiency. Diffusion-controlled delivery was indicated by release following first-order and Higuchi kinetics, although super case-II transport was suggested by Korsmeyer-Peppas analysis (n = 1.105). The cream showed moderate tyrosinase inhibition, TNF-α expression suppression, and non-cytotoxic behavior.

CONCLUSION: Ferulic acid's potential as a safe and efficient cosmeceutical for skin-brightening applications is supported by the cubosomal cream's significant improvements in solubility, photostability, and prolonged dermal application.