Preparation And Evaluation Of Sustained Nanoparticles Encapsulating Triamcinolone Acetonide And Mycophenolate Mofetil For Thyroid Associated Ophthalmopathy

In recent years,nano drug carriers have been widely used in the biomedical field with strong tissue permeability and high biofilm adhesion.They can not only improve the solubility,stability and targeting ability of drugs,but also prolong and control the drug release.Polyethylene glycol(PEG)-poly lactic-glycolic acid(PLGA)has good biocompatibility and has been served as the carrier material for a variety of drug preparations.Traditional drug therapy for thyroid-associated ophthalmopathy(TAO)is encountered with problems,such as frequent administration during the treatment,various adverse events and poor patient compliance.The development of novel pharmaceutical preparations for TAO may improve the therapeutic effect and realize a specific,safe and efficient treatment patterns.In this study,sustained-release PEG-PLGA nanoparticles(PEG-PLGA-NPs)encapsulating triamcinolone acetonide(TA)and mycophenolate mofetil(MMF)for the treatment of TAO were prepared and the optimal preparation process and the in vitro release properties of the prepared nanoparticles(NPs)were discussed.In addition,the safety of two kinds of sustained-release NPs for the treatment of TAO was also tested.The main research contents and results are as follows:(1)Triamcinolone acetonide-loaded nanoparticles(TA NPs)and mycophenolate mofetil-loaded nanoparticles(MMF NPs)were prepared by emulsion solvent evaporation method with PEG-PLGA as raw material.(2)Single-factor experiments were used to determine the best conditions for the preparation of two kinds of NPs taking the particle size,zeta potential and encapsulation efficiency as investigation indicators and the preparation process was optimized.(3)Under the optimal conditions(with a stirring speed of300rpm),the average particle sizes of PEG-PLGA-NPs encapsulating TA and MMF were 604 nm and 589 nm,respectively,and the average zeta potentials were-8.77 mv and-6.92 mv,respectively.The average encapsulation efficiency of TA-NPs was 47.66% and the average encapsulation efficiency of MMF-NPs was 16.52%.The surface morphology of these two kinds of NPs was spherical with uniform size observed by transmission electron microscopy(TEM).(4)In vitro release experiments showed that the initial drug release rate of TA-NPs and MMF-NPs was not high and drugs were stably released for more than 3 weeks,achieving sustained and controlled drug release.(5)Through the in vitro cytotoxicity test,the safety evaluation of PEG-PLGA-NPs encapsulating TA and MMF found that the cell viability of groups co-culturing with TA-NPs or MMF-NPs was significantly better than that of cell groups treated with active pharmaceutical ingredient.This study verifies that the prepared PEG-PLGA-NPs encapsulating TA and MMF have simple preparation process,outstanding ability of drug loading and sustained release and good safety.Consistent with the requirements for clinical drug therapy,they might be used as potential therapeutic agents in the treatment of TAO.