Research Of Triamcinolone Acetonide Acetate(TAA) Thermosensitive Hydrogel For Intra-articular Injection

Rheumatoid arthritis(RA)is a autoimmune inflammatory disease whose main clinical manifestations are chronic,symmetry,synovial arthritis and joint disease.The basic pathological change is synovial inflammation,and then it causes bone damage and bone erosion.In later period,it may causes joint deformity with serious damage.Triamcinolone acetonide acetate(TAA)is a long-term glucocorticoid which can obviously inhibit articular synovial tissue and tumor necrosis factor secretion of interleukin-1 and TNF-? to reduce the proliferation of capillaries and fibroblasts.Its anti-inflammatory works fast and strong which can significantly improve the illness.TAA commercially available suspension preparation has short duration of efficacy and short residence time in articular cavity.So it must doses frequently which causes more and more adverse drug reactions and limits its clinical application.This topic studies the preparation of triamcinolone acetonide acetate(TAA)thermosensitive hydrogel in order to extend the residence time at injection site,reduce the drug times and adverse drug reactions,and to improve the bioavailability of drug,reach the role of local drug delivery and drug slow release.This study take PLGA-PEG-PLGA as gel matrices,xanthan gum as suspending agent and Nacl as flocculant to prepare TAA suspending thermosensitive hydrogel.The study chooses thermostatic mixing method to prepare the thermosensitive hydrogel.,The research uses the single factor investigation to determine the prescription of each component in the appropriate concentration range.Then the orthogonal test can be taken to determine the optimal prescription.After needle test,sedimentation volume ratio test,and then dispersion test to determine the best prescription and its gelling temperature is 35.3 ?.A quality control method of estradiol were established.A quantitative HPLC method were used to determine the estradiol contents in TAA thermosensitive hydrogel.This method had good specificity,high precision and good stability.The in vitro test took 0.9% sodium chloride solution containing 2% SDS which can meet the conditions of slot leakage as release medium for no film release.The accumulative drug release was up to 83.31% in 16 days.The dug release follows Ritger-Peppas mathematical model:Q=0.0021t1/2-0.0002,R2=0.9980.With appearance,gelling temperature and in vitro release as an index,preliminary stability test preparation was evaluated by factor experiment and long-term experiments.The result confirmed that high temperature had a great influence on the stability of the TAA thermosensitive hydrogel.And the temperature and illumination test result suggested that freezing the reagents should keep in cold storage and avoid light.Through the mouse's subcutaneous air bag in flammation model,give the different components with drug treatment to investigate their pharmacodynamics slow-release performance by comparing physical characteristics,tissue section and the level of inflammatory cytokines TNF-?.The pharmacodynamics' result shows that TAA thermosensitive hydrogel has stronger and longer inflammation inhibition than TAA commercially available suspension preparation.Finally,Ivis Lumina XR was applied to evaluated the retention of TAA thermosensitive hydrogel in KM mice after dosing 0 h,2 h,8 h,1 d,3 d,5 d,7 d and 9 d.The small animal in vivo imaging experimental result shows that TAA thermosensitive hydrogel's residence time can reach more than 9 days in the body.So it's very appropriate for intra-articular injection to achieve local slow-release.To sum up,TAA thermosensitive hydroge describied in this study has good temperature sensitivity,quality stability,strong and durable inflammation inhibition,Good slow-release effect and retention which is expected to become a new drug delivery system for intra-articular injection.