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The aim of this study was to develop hydrogel loaded with capsicum extract nanoparticles and wax gourd extract for transdermal delivery of capsaicin. The addition of wax gourd extract was supposed to reduce cytotoxicity of capsaicin in capsicum extract against HaCaT keratinocyte cell line. Capsicum extract nanoparticles were prepared by solvent displacement method using hyaluronic acid as a stabilizer. The physical and chemical stability of capsicum extract nanoparticles were investigated by dynamic light scattering technique and UV–Visible spectrophotometry, respectively. Hydrogel loaded with capsicum extract nanoparticles and wax gourd fruit extract was then formulated by using Carbopol 940® as a gelling agent for transdermal delivery. The skin permeability of capsaicin from the hydrogel was evaluated by Franz diffusion cell approach. The cytotoxicity reduction of capsicum extract nanoparticles and capsicum extract nanoparticles by mixing with wax gourd extract was determined by MTT assay The results showed that capsicum extract nanoparticles exhibited an average diameter of 168.4 ± 5.3 nm with a polydispersity index and zeta potential value of 0.26 ± 0.01 and −45.7 ± 7.1 mV, respectively. After two month-storage, particle size, polydispersity index, and zeta potential values of capsicum extract nanoparticles stored at 4° C, 30° C, and 45 °C did not significantly change. The capsaicin content decreased to 78%, 71%, and 72% when stored at 4 °C, 30 °C, and 45 °C for three months, respectively. The pH values of hydrogel containing capsicum extract nanoparticles were found to be in the range of 5.58–6.05 indicating good stability. The hydrogel exhibited a pseudoplastic character. The rate of permeation flux of capsaicin from hydrogel was 7.96 µg/cm2/h. A significant increase in cell viability was observed when the cells were incubated with capsicum extract nanoparticles mixed with wax gourd, compared to capsicum extract nanoparticles alone. The wax gourd extract in the hydrogel protected HaCaT cells from capsaicin cytotoxicity, thus may provide a new approach for delivery of capsaicin to reduce cytotoxicity to skin cells.  相似文献   
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