UNIGE document Scientific Article
previous document  unige:72989  next document
add to browser collection

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

Zuluaga, Maria-Fernanda
show hidden authors show all authors [1 - 9]
Published in European journal of pharmaceutics and biopharmaceutics. 2015, vol. 93, p. 110-117
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 systemMicroparticlesLiposomesPLGAPLAP38 MAPK inhibitorsIntra-articularLong-term release
PMID: 25836052
Full text
Article (Published version) (1.4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research groups Mécanisme de l'inflammation articulaire (44)
Technologie pharmaceutique
(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 https://archive-ouverte.unige.ch/unige:72989

567 hits



Deposited on : 2015-06-03

Export document
Format :
Citation style :