Poloxamer micellar system for intra-articular injection of 15-deoxy-Δ12,14-prostaglandin J2 with improved bioavailability and anti-inflammatory properties in the temporomandibular joint of rats

[Display omitted] Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. P...

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Published inInternational journal of pharmaceutics Vol. 583; p. 119383
Main Authors Abdalla, Henrique B., Napimoga, Marcelo H., Macedo, Cristina G., Bonfante, Ricardo, De Araujo, Daniele.R., de Mello, Nathalie F.S., Carvalho, Lucas B., Fraceto, Leonardo F., Clemente-Napimoga, Juliana T.
Format Journal Article
LanguageEnglish
Published Elsevier B.V 15.06.2020
Subjects
15d-PGJ2
Pain
Poloxamer micellar system
Temporomandibular joint
Temporomandibular joint
Pain
15d-PGJ2
Poloxamer micellar system
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Abstract [Display omitted] Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ.
AbstractList [Display omitted] Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ.
ArticleNumber 119383
Author Napimoga, Marcelo H.
De Araujo, Daniele.R.
Fraceto, Leonardo F.
Bonfante, Ricardo
Carvalho, Lucas B.
de Mello, Nathalie F.S.
Clemente-Napimoga, Juliana T.
Abdalla, Henrique B.
Macedo, Cristina G.
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  surname: Abdalla
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  givenname: Cristina G.
  surname: Macedo
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  organization: Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, Brazil
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  givenname: Leonardo F.
  surname: Fraceto
  fullname: Fraceto, Leonardo F.
  organization: Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, Brazil
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  givenname: Juliana T.
  surname: Clemente-Napimoga
  fullname: Clemente-Napimoga, Juliana T.
  email: juliana.napimoga@slmandic.edu.br
  organization: Faculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Laboratory of Neuroimmune Interface of Pain, Campinas 13045-755, Brazil
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Pain
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Snippet [Display omitted] Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes....
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SubjectTerms 15d-PGJ2
Pain
Poloxamer micellar system
Temporomandibular joint
Title Poloxamer micellar system for intra-articular injection of 15-deoxy-Δ12,14-prostaglandin J2 with improved bioavailability and anti-inflammatory properties in the temporomandibular joint of rats
URI https://dx.doi.org/10.1016/j.ijpharm.2020.119383
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