Brij® integrated bilosomes for improving the transdermal delivery of niflumic acid for effective treatment of osteoarthritis: In vitro characterization, ex vivo permeability assessment, and in vivo study

Bilosomes are innovative vesicular carriers containing bile salt with a non-ionic surfactant. Being highly flexible, bilosomes can squeeze themselves through the skin carrying the drug to the action site and improving its skin penetration. The objective of this research was to encapsulate niflumic acid (NA), a non-steroidal anti-inflammatory drug into Brij (R) integrated bilosomes (BIBs) for effective treatment of osteoarthritis through transdermal delivery. BIBs were formulated using 100 mg of Span 20 with different amounts of sodium cholate (NaC), sodium taurocholate (NaTC), or sodium glycocholate (NaGC) as bile salt, with the addition of 5 mg of Brij-93 or Brij-35. BIBs were prepared utilizing ethanol injection method with the application of (3(1) x 2(2)) complete factorial design using Design-Expert (R) software. The optimal BIBs formulation determined was (B5) which contains 5 mg of NaTC used as bile salt and 5 mg of Brij-93. B5 exhibited entrapment efficiency% = 95.21 +/- 0.00%, particle size = 373.05 +/- 0.07 nm, polydispersity index = 0.27 +/- 0.01, and zeta potential = -32.00 +/- 0.00 mV. It also had a high elasticity with a spherical shape. B5 gel displayed a sustained release profile with a significantly 2.3 folds' higher drug permeation percent across rat skin than that permeated from NA gel. Moreover, in vivo anti-osteoarthritic and histopathological studies assured the efficacy and safety of B5 gel and its superiority over NA gel. Generally, the outcomes confirmed the great efficacy of NA loaded BIBs for the topical treatment of osteoarthritis.

Automated summary

The objective of this research was to encapsulate niflumic acid into bilosomes for transdermal delivery and effective treatment of osteoarthritis. The optimal formulation (B5) contained 5 mg of sodium taurocholate and 5 mg of Brij-93, showing high entrapment efficiency and suitable particle size. B5 gel exhibited higher drug permeation across rat skin compared to NA gel and demonstrated superior efficacy in vivo.