RESUMO
Objective To construct oligomeric hyaluronic acid(5 KDa)-modified ellagic acid-loaded liposomes(EA-HA-L)to improve the aqueous solubility,in vitro transdermal effect and whitening activity of ellagic acid.Methods Oligomeric hyaluronic acid-modified cholesterol(HA-Chol)was prepared by esterification reaction and structurally characterized by FTIR and 1H NMR;Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes were prepared by film dispersion-ultrasound method,and the prescribing process was optimized by Box-Behnken design-response surface method,and the particle sizes,the polydispersity index(PDI),zeta potential and encapsulation rate of liposomes under the optimal prescribing process were determined;the difference in solubility between EA-HA-L and free EA was evaluated;in vitro transdermal effect of liposomes were investigated using rat abdominal skin;inhibitory effect on tyrosinase and intracellular tyrosinase in mouse melanoma cells(B16-F10)was surveyed via dopa oxidation method.Results HA-Chol was synthesized and characterized;the optimized prescription process was mass ratio of 10:1 for soy phospholipids to HA-Chol,lipid-drug ratio of 40:1,hydration temperature of 30℃,hydration time of 60 min,ultrasound intensity of 35％,ultrasound time of 21 min,and the particle size of EA-HA-L produced under the optimized prescription process was(140.30±1.30)nm,PDI was(0.29±0.01),the encapsulation rate of ellagic acid was 91.16％±3.06％,and the zeta potential was(-5.67±0.09)mV;after EA was encapsulated by liposomes,the solubility of EA in water increased by about 40-fold;the cumulative transdermal amount of EA-HA-L was 46.98±2.17 μg·cm-2 in 24 h,and the intradermal retention was 66.15±0.61 μg·cm-2,which was 1.72 times higher than that of free EA(P<0.0001)and 1.23 times higher than plain liposome(EA-L)(P<0.01);and the tyrosinase inhibitory activity of EA-HA-L was higher than that of both free EA and EA-L in the EA concentration range of 50-400 μg·mL-1.Conclusion Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes with small particle size and high encapsulation rate were successfully prepared.EA-HA-L significantly improved the water solubility of EA and possessed better transdermal effect and stronger whitening activity than free EA and EA-L.
RESUMO
Objective With the improvement of people's living standards, people's requests for beauty are increasing. Skin whitening and lightening have become the pursuit of many women, and whitening and removing freckles have become the focus of scientific research. At present, widely used whitening agents, such as kojic acid, vitamin C, and its derivatives, have shortcomings such as poor stability and retarded effect. Therefore, safer and more effective whitening products from herbs are urgently needed. To explore the possibility of triterpenes as whitening active substance, the effects of total triterpenes of Poria (TTP) and poricoic acid A (PAA) on mushroom tyrosinase activities and B16 cells were investigated, and their mechanisms on mushroom tyrosinase were also studied. Methods Using arbutin and nicotinamide as reference substances, we determinated the inhibitory effects of TTP and PAA on mushroom tyrosinase and tyrosinase in B16 cells and then studied the inhibitory mechanism on mushroom tyrosinase. Results TTP and PAA exhibited good inhibitory effects on the activities of monophenolase and diphenolase in mushroom tyrosinase, as well as a certain inhibitory effect on tyrosinase in B16 cells. Conclusion TTP and PAA are potential whitening active ingredients.