Study Of Retinyl Propionate Delivery Emulsion Construction And Its Skin Anti-photoaging Effect

Retinyl propionate is a retinol derivative commonly used as anti-aging ingredient to solve skin aging or photoaging.Structurally,retinyl propionate has all-trans conjugated double bonds,which are easily affected by environmental factors such as ultraviolet rays,high temperature,and reactive oxygen species and thus inactivated.Meanwhile,its high lipophilic property makes it almost impermeable within the stratum corneum.Therefore,the application of retinyl propionate in skin was limited because of low stability and low permeability.Although a series of retinol encapsulated compounds have been developed in recent years to maintain their activity,some encapsulation methods have not been widely used due to complex preparation processes and low loading capacity.And there are few studies on retinyl propionate encapsulated compounds.In addition,the use of high dose retinyl propionate on senescent cells can cause oxidative stress damage.And decreased content of oxidized coenzyme I(NAD~+)in senescent cells may limit the conversion of retinyl propionate to retinoic acid.Flavonoids have the potential to relieve oxidative stress and increase intracellular NAD~+levels.Based on this,this study aims to prepare simple and skin-friendly oil-in-water emulsion to stable retinyl propionate.Flavonoids are used to synergize retinyl propionate during delivery to the deeper dermal layer to enhance skin anti-photoaging properties.The main contents and conclusions are as follows:(1)The stability of retinyl propionate in emulsions was enhanced using lamellar gel phase formed by ceteareth-20,cetearyl alcohol and stearyl alcohol.The pseudo-ternary phase diagram constructed from ceteareth-20,mixed fatty alcohols(cetearyl alcohol/stearyl alcohol molar ratio1/1)and water showed that lamellar gel phase was formed between ceteareth-20/mixed fatty alcohol molar ratio of 1/2-1/10.The lamellar gel emulsion constructed by molar ratio of 1/6 had the best effect on stabilizing low-loaded retinyl propionate,and its retention ratio after 30 days in storage at 50°C was(80.8±5.0)%.The effects of carrier oil type and content on retinyl propionate were discussed under this molar ratio.It was found that the polarity of pentaerythritol tetraethylhexanoate was similar to that of retinyl propionate,and the addition of9%pentaerythritol tetraethylhexanoate improved the retention ratio and loading capacity of retinyl propionate in emulsion.In vitro Franz transdermal experiments showed that emulsions containing lamellar gel phase could significantly enhance the transdermal delivery of retinyl propionate.(2)The protective effect of nanoemulsions constructed from the main emulsifier inulin lauryl carbamate on retinyl propionate was investigated.The results of orthogonal experiments showed that the optimal content of emulsifiers in nanoemulsion was:3.34%inulin lauryl carbamate,5%polysorbate-20,0.5%behentrimonium chloride.Stability experiments showed that the retention ratio of nanoemulsions containing 1%and 5%retinyl propionate was both higher than 80%after 30 days when storage at 50°C.The stability and anti-coalescence properties of this nanoemulsion can be attributed to the synergistic effect of three emulsifiers,which led to the formation of densely-packed,sterically-hindered and highly-charged interfacial layers at the oil-water interface.The content of retinyl propionate in epidermis and dermis layer of nanoemulsion was about 10 and 46 times respectively that of conventional oil-in-water emulsion.Retinyl propionate loaded nanoemulsion had significant proliferative ability on human fibroblasts,and its cell proliferation rate increased by about 26%.(3)UVA senescence fibroblast model was established,and the effect of quercetin on retinyl propionate against cellular photoaging was investigated.Based on the results of cell viability and the expression ofβ-galactosidase,the aging model was established by irradiating fibroblasts at a dose of 15 J/cm~2 UVA.The proliferation rate of UVA senescent fibroblasts in the combination of 2μg/m L quercetin and 5μg/m L retinyl propionate had a significant promoting effect,and the proliferation rate was increased by about 13.31%compared with the UVA model group.The composition of quercetin and retinyl propionate effectively alleviated UVA-induced fibroblast aging,significantly inhibited the accumulation of reactive oxygen species in cells,the secretion of matrix metalloproteinase-1,and increased the content of type Ⅰ collagen.(4)The effects of quercetin and retinyl propionate compositions on UVA senescent cell signaling pathways were further analyzed.The results of western blot and immunofluorescence staining showed that quercetin/retinyl propionate composition inhibited nuclear transfer of p65subunit of the NF-κB pathway and inhibited phosphorylation of JNK and c-Jun proteins.In addition,quercetin increased intracellular NAD~+content after UVA irradiation in a dose-dependent manner.The results of molecular docking showed that quercetin may affect the conversion of retinyl propionate by competitively inhibiting CD38 enzyme and PARP-1enzyme activities to increase NAD~+levels.The above results showed that quercetin/retinyl propionate composition may alleviate UVA-induced fibroblast photoaging effects through multiple pathways.