Innovative technologies for investigating chayote (Sechium edule (Jacq.) Swartz) peel's nutritional and economical valorization are required. This study aimed to extract bioactive compounds from chayote peels, comparing four sustainable extraction techniques: subcritical water extraction (SWE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and maceration (ME).

The obtained extracts were analyzed for their phenolic and carotenoid contents using High-Performance Liquid Chromatography (HPLC) and screened for their potential anti-inflammatory activity via the protein denaturation assay, and antioxidant activity through DPPH, ABTS, and FRAP in vitro assays. Based on these bioactivities, and after assessing cytotoxicity on Caco-2 cells, the most promising extract was used to formulate an ethosomal gel. Ethosomes were prepared by a solvent dispersion technique comprising 2% phospholipids, 20% ethanol, 2% lyophilized chayote peel extract, and an aqueous phase of 100% (w/w). Carbopol 934 was used to prepare the ethosomal gel. Test and control formulations were evaluated for pH, conductivity, rheology, and physical stability over one month at 4 °C and 25 °C.

The results showed that the UAE approach was more effective inextracting phenolics and carotenoids from chayote peels. AnHPLC analysis of the UAE extract identified tocopherol esters as the main class of carotenoids, and phenolics such as 4-hydroxyphenylacetic acid, gallic acid, protocatechuic acid, ferulic acid, p-coumaric acid, myricetin, and quercetin. At a concentration of 1000 µg/mL, the UAE extract showed a slight but significant decrease in cell metabolic activity, reducing MTT to 91.6% and 91.5%. A stable ethosomal gel containing the UAE chayote peel extract was successfully developed and characterized for its cosmeceutical potential. The gel demonstrated good physical stability after one month of storage at both 4 °C and 25 °C.