Abstract:

Objective To discuss the optimal preparation process and the in vitro release properties of the poly （lactic-co-glycolic acid）poly（ethylene glycol）（PEG-PLGA） nanoparticles of triamcinolone acetonide（TA） and mycophenolate mofetil（MMF） in the treatment of thyroid associated ophthalmopathy（TAO）， and to evaluate its safety in the treatment of TAO by periorbital injection. Methods The TA nanoparticles （TA NPs group） and MMF nanoparticles （MMF NPs group） were prepared with PEG-PLGA as the raw material by emulsification method. The process optimization was carried out with the encapsulation efficiency as the evaluation indicator. The morphology of nanoparticles in various groups was observed under transmission electron microscope；the sizes of nanoparticles in various groups were detected by zetasizer particle size and potential analyzer. The release properties of nanoparticles in various groups were detected by ultraviolet spectrophotometry in vitro and the release rates of the drug were calculated，and then the release properties of the drugs were analyzed on the basis of clinical medication rules. The human retinal pigment epithelial hRPF-19 cells were divided into blank control group，different concentrations of TA groups，different concentrations of MMF groups，different concentrations of TA NPs group， and different concentrations of MMF NPs groups.The viabilities of the cells were evaluated by MTT test and the safty of preparation was evaluated. Results The TA-loaded and MMF-loaded nanoparticles were prepared （TA NPs and MMF NPs）. The encapsulation efficiencies of TA NPs and MMF NPs were 47.66% and 16.52%， with an average particle size of 600 nm. The potential of the nanoparticles met the basic requirements of periorbital injection. Under the microscope， the TA NPs and MMF NPs showed round appearance and a high degree of uniformity. The detection results of drug release system in vitro showed that the release characteristics of TA-NPs and MMF-NPs met the administration characteristics of TAO treatment drugs and the sustained release was able to last more than 3 weeks. The initial release rate was low and the release curve was stable. The MTT results showed that there were no significant cell inhibitions in different concentrations of TA groups， MMF groups， TA NPs groups，and MMF NPs groups at the lower concentration. At the higher concentration，compared with same concentration of TA group， the viabilities of the cells in 40，80，and 160 nmol·L^－1 TA NPs groups were increased （P<0.01）； compared with same concentration of MMF group，the viabilities of the cells in 50，100，and 200 nmol·L^－1 MMF NPs groups were increased （P<0.01）. Conclusion The physicochemical parameters of TA NPs and MMF NPs meet the basic requirements for the periorbital injection with simple preparation process and good safety and have better drug-loaded and sustained release effects， which can be consistent with the requirements for clinical drug therapy in the treatment of TAO.

Key words: Thyroid-associated ophthalmopathy, Triamcinolone acetonide, Mycophenolate mofetil, Nanoparticles, In vitro release