Cyano-phycocyanin loaded enriched transfersomes for enhanced topical skin delivery and antioxidant protection

This study aimed to develop and evaluate cyano-phycocyanin (C-PC)-loaded enriched transfersomes for topical application, improved skin delivery, and antioxidant protection. The main objective was to overcome the limitations associated with C-PC's instability and poor skin permeability due to its high molecular weight and hydrophilicity. Six formulations were prepared using an organic solvent-free two-step method: glycerol-enriched transfersomes (Gly-transfersomes),glycerol and cholesterol-enriched transfersomes (Gly-chol-transfersomes),hyaluronate-enriched transfersomes (Hyal-transfersomes),hyaluronate and cholesterol-enriched transfersomes (Hyal-chol-transfersomes),glycerol and hyaluronate-enriched transfersomes (Hyal-gly-transfersomes), anda combination of all three (Hyal-gly-chol-transfersomes). Empty vesicles were prepared via direct sonication, then C-PC was gently loaded using mild sonication in a temperature-controlled ultrasonic bath. All formulations demonstrated properties suitable for skin delivery, with mean diameters <115 nm, polydispersity indexes <0.2, and zeta potential below -30 mV. Cryo- transmission electron microscopy confirmed spherical, unilamellar or oligolamellar morphology. Gly- and Gly-chol-transfersomes exhibited the highest encapsulation efficiency (∼52 %) and remained stable for up to 8 months at 4 °C. Antioxidant activity of C-PC (∼23-27 μmol TE/g of dry C-PC) was confirmed via DPPH assay. Biological tests on HaCaT cells exposed to H₂O₂-induced oxidative stress showed ∼80 % cell viability after treatment with C-PC formulations, compared to ∼60 % in untreated cells, indicating cytoprotective activity. Ex vivo skin penetration studies revealed significantly higher C-PC accumulation in the epidermis especially for Gly- and Gly-chol-transfersomes versus aqueous C-PC. These findings confirm the potential of enriched transfersomes as effective carriers to improve the skin delivery and bioactivity of C-PC in antioxidant skin care formulations.