Preparation And Evaluation Of Hyaluronic Acid Albumin Nanoparticles In Ophthalmic Drug Delivery System

ObjectiveIn recent years,due to factors such as excessive eye use,the use of electronic products,an aging population,and environmental degradation,the incidence of eye diseases has been increasing.Glaucoma,conjunctivitis,retinopathy and many other eye diseases,such as failure to timely and effective treatment will eventually have repeated attacks and even serious consequences of blindness.Constructing an eye drug delivery system,increasing the penetration rate of the drug eye barrier,and improving drug eye bioavailability are important research directions for the treatment of eye diseases.The vitreous body of the eye is rich in a large amount of hyaluronic acid.Hyaluronic acid has moisturizing and lubricating effects for eye administration;hyaluronic acid can also be used as a carrier material for the eye nanosystem and has good biocompatibility.In this paper,we designed and constructed albumin nanoparticles of water-soluble macromolecular hyaluronic acid,investigated the irritation of the nanoparticles to the eye and the accumulated amount of drugs in different parts of the eye,and evaluated their possibility as drugs and carriers for the treatment of eye diseases And scientific.MethodsThe methods for determining the content of hyaluronic acid(HA)and Rhodamine B(RhoB)by UV-Vis spectrophotometry and HPLC-FLD were established respectively;the particle size and Zeta potential were used as the inspection indicators,and the double-emulsion method was used Hyaluronic acid albumin nanoparticles(HA-BSA NPs),using water-W/O colostrum and emulsifier pseudo-ternary phase diagram to determine the ratio of different hydrophilic emulsifiers,system pH,W/O colostrum and the ratio of emulsifier.The pharmacological properties of particle size,morphology,encapsulation efficiency and drug loading were determined by dynamic laser scattering method,transmission electron microscope scanning method and microcolumn centrifugation method.Through the in vitro corneal penetration test,the corneal permeability of nanoparticles was investigated.Through intraconjunctival administration,Draize experiment and HE staining microscopic experiment,the eye irritation of nanoparticles was investigated.RhoB was used as a water-soluble fluorescent probe to investigate the content of HA-BSA NPs in different biological matrices in rabbit eyes at different times after intra-conjunctival administration.Confirm the ocular delivery process of the prepared nanoparticles.ResultsIt was determined that the compound emulsifier used to prepare HA-BSA NPs by double-emulsion method was sodium caseinate(SC)and poloxamer 188(F68),the ratio of the two was 3:2,and the pH of the system was 5.0 and 7.0.The prepared nanoparticles have a particle size of about 200 nm and a uniform distribution.The Zeta potential is about-19 mV and-40 mV,the encapsulation rate is greater than 85%,and the drug loading is greater than 5 μg/mg.The in vitro corneal permeability of the nanoparticles is about 1.8%.The results of the Draize eye irritation test and HE tissue staining test in rabbits show that there is no obvious abnormality in the eye tissues of rabbits after intra-conjunctival injection.Compared with the solution group,HA-BSA NPs loaded with RhoB fluorescent probes had increased accumulation in various parts of rabbit eye tissue after intra-conjunctival administration.Nanoparticles with a zeta potential of-40 mV had a significant effect on vitreous and lens Both have good delivery effects,and nanoparticles with a potential of-19 mV accumulate most in the cornea,and both nanoparticles are less distributed in the lens.ConclusionsThe double-emulsion method can be used for the preparation of water-soluble macromolecular nanoparticles,and nanoparticles with different Zeta potentials can be obtained by controlling the pH value of the system.The cornea is the main barrier for the transport of HA-BSA NPs into the eye.The prepared nanoparticles are less irritating to the eye by intraconjunctival administration.Intraconjunctival injection can effectively avoid the corneal barrier and reach the back of the eye(Vitreous,lens),the Zeta potential has a certain effect on the transport of nanoparticles in the eye tissue.When the Zeta potential is low(-40 mV),the nanoparticles accumulate more in the vitreous body and lens of the rabbit’s eye,which is expected to be used as an Drug loading system for treatment of posterior diseases.