en
Scientific article
English

Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system

Publication date2015
Abstract

In the treatment of arthritic diseases, oral or systemic administration of anti-inflammatory substances, such as p38 MAPK inhibitors, is hampered by numerous side effects. To overcome them, formulations of rapid and extended drug delivery systems were studied in intra-articular administration. For the first time, VX-745, a highly selective p38 MAPK inhibitor, demonstrated in vivo bioactivity, similar to dexamethasone activity, following intra-articular administration in an antigen-induced arthritic (AIA) mouse model. The in vitro bioactivity of VX-745 was also shown on synoviocytes, reducing the IL-6 concentration. Process and formulation parameters (i.e., polymer concentration, aqueous/organic phase ratio, emulsification speed and process, and evaporation pressure) and particle characterisation (i.e., drug loading, size of particle, and surface aspect) were extensively examined to produce optimised formulations. Indeed, a burst release provides a rapid saturation of intracellular p38 MAPK to relieve patients from pain and inflammation. Then, drug diffusion would be sufficient to maintain an effective dose over 2-3 months. This study confirms the effectiveness of encapsulated p38 MAPK inhibitors in extended drug delivery systems and seems to be a promising strategy for intra-articular treatment.

Keywords
  • Drug delivery system
  • Microparticles
  • Liposomes
  • PLGA
  • PLA
  • P38 MAPK inhibitors
  • Intra-articular
  • Long-term release
Citation (ISO format)
PRADAL, Julie et al. Intra-articular bioactivity of a p38 MAPK inhibitor and development of an extended-release system. In: European journal of pharmaceutics and biopharmaceutics, 2015, vol. 93, p. 110–117. doi: 10.1016/j.ejpb.2015.03.017
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Article (Published version)
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Identifiers
ISSN of the journal0939-6411
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Technical informations

Creation06/01/2015 11:42:00 AM
First validation06/01/2015 11:42:00 AM
Update time03/14/2023 11:21:02 PM
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