| ObjectiveMelatonin(MLT)is an amine hormone produced by mammals and human pineal gland.It has many physiological functions such as regulating the body’s biological clock,sedative hypnosis and immune regulation.In this paper,in order to avoid first-pass effect of oral administration,we used lecithin and cholesterol as carrier materials,and sodium deoxycholate as a softener was added in the film-forming material to prepare melatonin-loaded elastic liposome for transdermal administration.At the same time,it increases the solubility and the half-life and the bioavailability of the drug.A novel drug delivery system is provide a new treatment scheme for melatonin transdermal administration.MethodsIn this study,melatonin was used as a model drug,lecithin and cholesterol were used as carrier materials and sodium deoxycholate as a softener.The basic physicochemical properties of melatonin were studied by HPLC.Formulation was optimized via the central composite design method.In vitro permeable experiments on isolated skin of mice was carried out using a vertical Franz diffusion device.The photoaging model of mice was established by ultraviolet irradiation to explore the anti-skin photoaging effect.SD rats were used to investigate the pharmacokinetic character of the elastic liposomes after percutaneous absorption.C57BL/6 mice were used to investigate dynamic changes in phagocytosis of Langerhans cells.ResultsThe results of the prescriptions optimized by Design-Expert software showed that melatonin was 18.90mg,lecithin was 80.00mg,cholesterol was 20.00mg and sodium deoxycholate was 18.91mg.The PS,PDI,EE and DL of elastic liposomes prepared with this prescription were 48.87nm,0.203,73.91% and 9.92%,respectively.The results of FTIR,DSC and XRD showed that the chemical structure of melatonin was not changed after prepared elastic liposomes,and the drug was successfully encapsulated in the elastic liposomes membrane material.The results of permeation experiments showed that the cumulative penetration of elastic liposomes was 1.5 times higher than that of ordinary liposomes,indicated that the elastic liposomes more easily penetrated into the body.And pharmacokinetic experiments in rats showed that the AUC of the elastic liposomes was 1.82 times higher than that of the common liposomes,indicated that elastic liposomes could improve the bioavailability of melatonin percutaneous absorption.The pharmacodynamic experiments showed that the liposomes preparation had anti-aging effect.The experiments of the permeation mechanism of melatonin showed that the elastic liposomes entered the skin could changed the structure of the stratum corneum lipid and keratin,and the amount of phagocytosis was different by the Langerhans cells.ConclusionThe melatonin elastic liposomes prepared by the film dispersion method has a small particle size and PDI,a high encapsulation efficiency and drug loading,and a good physical and chemical properties.Through transdermal mechanism studies,it has been confirmed that percutaneous penetration of liposomes can alter the structure of skin stratum corneum lipids and keratin,and can be phagocytosed by Langerhans cells.Through pharmacokinetic and pharmacodynamic experiments proved that compared with ordinary liposomes,melatonin elastic liposomes were more likely to penetrate into the skin to exert effects,improve bioavailability,and has the effect of anti-photoaging.This effects provides some theoretical basis for the prevention and treatment of melatonin against skin lesions caused by ultraviolet sunburn. |
