Oleuropein multicompartment nanovesicles enriched with collagen as a natural strategy for the treatment of skin wounds connected with oxidative stress.

Collagen-enriched transfersomes, glycerosomes and glytransfersomes were specifically tailored for skin delivery of oleuropein. Vesicles were prepared by direct sonication and their main physicochemical and technological properties were measured. Biocompatibility, protective effect and promotion of the healing of a wounded cell monolayer were tested using fibroblasts. Vesicles were mainly multicompartment, small (∼108 nm), slightly polydispersed (approximately 0.27) and negatively charged (~-49 mV). Oleuropein was incorporated in high amounts (approximately 87%) and vesicles were stable during four months of storage. studies confirmed the low toxicity of formulations (viability ≥95%), their effectiveness in counteracting nitric oxide generation and damages caused by free oxygen radicals, especially when collagen glytransfersomes were used (viability ~100%). These vesicles also promoted the regeneration of a wounded area by promoting the proliferation and migration of fibroblasts. Collagen-enriched vesicles are promising formulations capable of speeding up the healing of the wounded skin.