A novel Te-ethosomes-loaded thermosensitive gel for enhanced transdermal delivery and melasma therapy.

The therapeutic potential of tectoridin for melasma treatment is limited by its poor aqueous solubility. To address this limitation, we developed tectoridin-loaded ethosomes using the film dispersion method, and optimised the formulation via orthogonal design, before incorporation of these ethosomes into a gel. The optimised tectoridin ethosomes showed a spherical morphology with uniform dispersion, a particle size of 197.84 ± 1.43 nm, a zeta potential of -22.75 ± 0.61 mV, a polydispersity index of 0.209 ± 0.05, an encapsulation efficiency of 92.82 ± 0.16%, and a drug loading of 9.75 ± 0.05%, thereby demonstrating good storage stability for 30 days at both 4 °C and 25 °C. The resulting Tectoridin (Te)-Ethosomes-Loaded Thermosensitive Gel (Te-ethosomes@Gel) exhibited suitable rheological properties, erosion rate and in vitro release profile. Both ethosomes and the gel enhanced drug release, cellular uptake and safety. All tectoridin formulations significantly inhibited tyrosinase activity, reduced melanin content and deposition in PIG1 cells and suppressed the expression of transcription of tyrosinase, TRP1, MITF, Myosin Va, Rab27a, Cdc42, p-p38 and p-ERK proteins. In vivo pharmacodynamic studies in a rat model of melasma further demonstrated that the Te-ethosomes@Gel significantly improved skin pigmentation, reduced oxidative stress markers and restored normal skin histology, with effects superior to those of free tectoridin or ethosomes alone. These findings demonstrate that Te-ethosomes@Gel offers a promising novel strategy for treating melasma.