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Title: Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration
Author: Guilherme, Viviane A.; Abdalla, Henrique B.; Bonfante, Ricardo; Cereda, Cintia M. S.; De Paula, Eneida; Ribeiro, Lígia N. M.; Alcântara, Ana C. S.; Castro, Simone R.; Rodrigues Da Silva, Gustavo H.; Da Silva, Camila Gonçalves; Breitkreitz, Márcia C.; Clemente-napimoga, Juliana; Macedo, Cristina G.
Year: 2019
Is part of: Scientific Reports, v. 9, p. 1 - 11
DOI: https://doi.org/10.1038/s41598-019-47486-w

Citation: Guilherme, Viviane A.; Abdalla, Henrique B.; Bonfante, Ricardo; Cereda, Cintia M. S.; De Paula, Eneida; Ribeiro, Lígia N. M.; Alcântara, Ana C. S.; Castro, Simone R.; Rodrigues Da Silva, Gustavo H.; Da Silva, Camila Gonçalves; Breitkreitz, Márcia C.; Clemente-napimoga, Juliana; Macedo, Cristina G.; Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration. Scientific Reports, v.9, p. 1-11, 2019

Abstract: Inflammatory conditions of the temporomandibular joint (TMJ) and peripheral tissues affect many people around the world and are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (2(3)) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25 degrees C. In vivo results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1 beta and TNF-alpha), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.

Keywords: antiinflamatory; drug delivery systems; nanostructed lipid carriers; naproxen;
Subjects: CIENCIAS_BIOLOGICAS; Farmacologia Bioquímica e Molecular;


Funding: The authors are grateful to Espaco da Escrita/Unicamp for translation services. The study was supported by FAPESP (#13/10766-0, #14/14457-5) and INCT-Bioanalitica/Unicamp.
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