Topical delivery of 3,5,4′-trimethoxy-trans-stilbene-loaded microemulsion-based hydrogel for the treatment of osteoarthritis in a rabbit model
The aim of this study was to develop a microemulsion-based hydrogel (MBH) formulation of 3,5,4′-trimethoxy-trans-stilbene (BTM) as topical delivery system for the treatment of osteoarthritis (OA). The pseudo-ternary phase diagrams were constructed to optimize the microemulsion (ME) formulation. The ME formulation containing 18.8% Cremopher EL35 (surfactant), 9.4% Transcutol HP (co-surfactant), 3.1% LABRAFIL M 1944 CS (oil), and 68.7% water was selected. The obtained BTM-loaded ME (BTM-ME) had a spherical morphology (17.5 ± 1.4 nm), with polydispersity index (PDI) value of 0.068 ± 0.016 and zeta potential of − 11.8 ± 0.5 mV, and was converted into BTM-loaded MBH (BTM-MBH) using Carbopol 940. Ex vivo skin permeation study showed that both ME and MBH formulations significantly enhanced the amount of BTM permeated. The cumulative amount of BTM permeated after 12 h (Q12) for ME, and MBH formulations were 3.25- and 1.96-fold higher than that for emulsion gel (EG). Pharmacokinetic study showed that the AUC of BTM suspension (oral) was three times higher than that of BTM-MBH (topical). Topical delivery of BTM-MBH demonstrated remarkable anti-OA effect in a rabbit model of OA induced by papain, with decreased levels of pro-inflammatory cytokines. The developed MBH formulation might be a promising strategy for topical delivery of BTM for treatment of OA.
KeywordsMicroemulsion Drug delivery system Transdermal Morphology Permeability
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All animal procedures in this study were approved by the Animal Ethical Experimentation Committee of The Second Xiangya Hospital of Central South University (Protocol number SYXK-2012-003). The institutional and national guidelines for the care and use of laboratory animals were followed.
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