{'fraction_non_alphanumeric': 0.038766519823788544, 'fraction_numerical': 0.015418502202643172, 'mean_word_length': 5.056, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Hyaluronic acid/parecoxib-loaded PLGA microspheres for therapy of temporomandibular disorders.

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 so as to solve the issues of poor drug delivery and short duration on drug concentration in conventional TMD therapy.


METHOD
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 be-havior of microspheres and toxicity assay on synovial cells were investigated. The in vitro anti-inflammatory effect on in-flammatory 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 morphological 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 ex-pression 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 significantlyreduced 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.