Objective: This study aimed to fabricate Hyaluronic Acid (HA)/parecoxib-loaded PLGA
microspheres for the treatment of Temporomandibular Disorders (TMD) and investigate the in
vitro and in vivo effect of the microsphere system to solve the issues of poor drug delivery and
short duration on drug concentration in conventional TMD therapy.
Methods: The microspheres were prepared by the double emulsion (w/o/w) method. Various formulations
were compared in terms of particle size, drug loading rate and encapsulation rate. Scanning
Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and FT-IR spectroscopy
were performed to evaluate physicochemical properties. The drug release behavior of microspheres
and toxicity 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.
Then, the in vivo therapeutic effect of microspheres was investigated using mechanically-induced
rat synovitis model. Protein levels of inflammatory cytokines (IL-1β, TNF-α and COX-2) from
TMJ periarticular tissues were quantified by Enzyme-Linked Immunosorbent Assay (ELISA).
Results: The results showed that microspheres were morphologically regular, smooth and non-cohesive.
The average particle size of the microspheres was (25.32 ± 1.01) μm. The drug loading rate
of parecoxib was 17.12%-20.95% with encapsulation efficiency reaching 51.9%-54.7%. 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 HA/parecoxib-loaded PLGA microspheres declined the mRNA
expression of IL-1β, TNF-α and COX-2 induced by LPS in articular synovial cells. Moreover,
in vivo results demonstrated that the intra-articular microspheres significantly reduced protein levels
of inflammatory cytokines (IL-1β, TNF-α and COX-2) for more than two weeks and stopped
the mechanically-induced synovitis in its tracks in rat models.
Conclusion: The study presented new and potential insights into treatments of TMD using PLGA
microspheres loaded with HA and parecoxib as a successful drug delivery system.