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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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General Research Article

Hyaluronic Acid/Parecoxib-Loaded PLGA Microspheres for Therapy of Temporomandibular Disorders

Author(s): Dongwang Zhu, Haoran Bai, Wanning Xu, Wen Lai, Liting Song and Jiayin Deng*

Volume 18, Issue 2, 2021

Published on: 17 August, 2020

Page: [234 - 245] Pages: 12

DOI: 10.2174/1567201817999200817151048

Price: $65

Abstract

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.

Keywords: Parecoxib, hyaluronic acid, PLGA microspheres, intra-articular injection, temporomandibular disorders, TNF.

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