Study On Optimization Of PLGA Nanoparticles Loaded With Astaxanthin And Evaluation Of Anti-photodamage Effect In Vitro

As the increasing of environmental pollution,the ozone layer is destroyed,more and more ultraviolet rays are irradiated to the ground.Excessive exposure to UV radiation(especially UVB)can produce large amounts of ROS,causing skin photoaging and even cancer.Astaxanthin is a xanthophyll carotenoid with superior antioxidant,anti-inflammatory and anti-cancer activities.However,since astaxanthin is poorly soluble in water,its stability is poor,and bioavailability is greatly reduced,so its application is limited greatly.Polylactic acid-glycolic acid copolymer(PLGA)is widely used as a carrier material for drug delivery systems with good biocompatibility.In this study,astaxanthin was loaded into PLGA nanoparticles and its physical and chemical properties were investigated.At the same time,UVB-induced Ha Ca T cell photodamage model was established to investigate the protection of astaxanthin and PLGA-loaded astaxanthin nanoparticles on photodamage model.The main research contents and results are as follows:(1)Based on the particle size,encapsulation efficiency and drug loading of nanoparticles,the single-factor experimental design was used to determine the range of conditions which affect the preparation of astaxanthin-loaded PLGA nanoparticles.The Plackett-Burman experimental design found out the key influencing factors;finally using the four-factor three-level Box-Behnken experimental design to obtain the optimal prescription of PLGA-loaded astaxanthin nanoparticles.(2)The optimum process conditions for the synthesis of astaxanthin-loaded PLGA nanoparticles with a particle size of 154.4±0.35 nm,and the zeta potential was-22.07±0.93 m V,the encapsulation efficiency was 96.42±0.73%,and the drug loading was 7.19±0.12%.The surface morphology was a uniform spherical shape.The physicochemical properties of the astaxanthin were successfully physically loaded into the PLGA nanoparticles.(3)In vitro antioxidant and water solubility experiments,astaxanthin-loaded PLGA nanoparticles still had antioxidant capacity,probably because astaxanthin could not be completely released at the beginning,so the rate of free radical scavenging of by PLGA-loaded astaxanthin nanoparticles was lower than astaxanthin.(4)Finally,the UVB photodamage model of Ha Ca T cells was established to investigate the antioxidant capacity of astaxanthin and astaxanthin-loaded PLGA nanoparticles at the cellular level.It was found that astaxanthin and astaxanthin-loaded PLGA nanoparticles can resist UVB-induced photodamage by reducing ROS production and restoring mitochondrial membrane potential.It was indicated that astaxanthin-loaded PLGA nanoparticles can be considered as a potential therapeutic agent for skin photoaging.