| Objectives: Temporomandibular disorders(TMD)is one of the most common diseases in oral and facial regions,which consists of clinical symptoms such as muscle pain,abnormal joint tone and jaw movement abnormalities.At present,for patients with TMD pain,intra-articular injection of local anesthesia drugs,nonsteroidal anti-inflammatory drugs,hormones or hyaluronic acid all have positive effects.As a new non-steroidal antiinflammatory drug,parecoxib is also a strong cyclooxygenase-2(COX-2)inhibitor,which has attracted extensive attention in clinical practice.Due to its good analgesic effect,high tolerance and small side effects,it is widely used in the treatment of various types of arthritis throμgh intra-articular injection.In addition,hyaluronic acid(HA)is one of the most commonly used drugs for intra-articular injection in clinical practice currently.Compared with other drugs,the injection of hyaluronic acid into the articular cavity is very safe and effective with few side effects.However,due to the complexity of the anatomical structure in the temporomandibular joint cavity,the stability of simple injection of the drugs is poor,the action time is short,and it is prone to degrade.Therefore,it often requires repeated injection,which not only increases the financial burden on patients but also increases the incidence of complications.In current years,with the development of biological science and technology,the fabrication of sustained-release microspheres using biodegradable polymer materials as carriers is getting more and more attention from researchers.lactic acid/glycolic acid copolymer(PLGA)has been approved of clinical application by the United States Food and Drug Administration(FDA)because of its good biological compatibility.Due to its good biocompatibility,controllable degradation rate and high targeting,PLGA has been widely used in carrier materials for controlled release in recent years.In this study,it is proposed to use PLGA as the carrier material to prepare parecoxibHA loaded PLGA microspheres.Thus,the controlled release of drugs can be realized,and new ideas and means for the treatment of TMD can be explored.Methods: 1.We prepare to use PLGA as the carrier material to prepare parecoxib-HA loaded PLGA microspheres using double emulsion and solvent evaporation method.2.Various formulations were compared in terms of particle size,drug loading rate and encapsulation rate.The preparation conditions of sustained-release microspheres were optimized,which included the molecular weight of PLGA,the concentration of polyvinyl alcohol,and the ratio of internal and external water phases.Scanning electron microscopy(SEM),differential scanni-ng calorimetry(DSC)and fourier transform infrared spectroscopy(FTIR)were performed to evaluate physicochemical properties.3.The in vitro release of the microspheres in the releasing mediμm was measured,and the cumulative drug release curve of the microspheres was drawn.4.CCK-8 assay on synovial cells were investigated.The in vitro anti-inflammatory effect on inflammatory markers such as IL-1β,TNF-α and COX-2 was assessed by real-time PCR.Results: The results showed that microspheres were morphological regular,smooth and noncohesive.The average particle size of the microspheres was 19.88 μm.The drug loading rate of parecoxib was 22.20 % with encapsulation efficiency reaching 56.13%.In vitro drug release tests showed a successful sustained release over 28 days with a burst of 19.98% of the total drug substance.Treatment with parecoxib/HA loaded PLGA microspheres declined the m RNA expression of IL-1β,TNF-α and COX-2 induced by LPS in synovial cells.Conclusion: In summary,the microspheres prepared in this study have smooth surface,high drug loading and encapsulation rate,obvious in vitro sustained release effect,and good in vitro anti-inflammatory activity,which presented new and potential insights into treatments of TMD. |
