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® 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 (31 × 22) complete factorial design using Design-Expert® 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.

Use of Novasomes as a Vesicular Carrier for Improving the Topical Delivery of Terconazole: In Vitro Characterization, In Vivo Assessment and Exploratory Clinical Experimentation.

PURPOSE: This manuscript aimed at encapsulating an antifungal terconazole (TCZ) into innovative novasomes for improving its penetration into the skin and clinically modulating its therapeutic efficacy. METHODS: Novasomes containing free fatty acid (FFA) as a penetration enhancer were formulated using ethanol injection technique based on 24 full factorial design to explore the impact of various formulation variables on novasomes characteristics regarding entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formulation was chosen using Design-Expert® software and utilized for further explorations. RESULTS: The chosen formulation (N15; including 100 mg lipid components and Span 80 to oleic acid in a ratio of 2:1 (w/w)) exhibited an EE% = 99.45 ± 0.78%, PS = 623.00 ± 2.97 nm, PDI = 0.40 ± 0.04, and ZP = -73.85 ± 0.64 mV. N15 showed spherical vesicles with a higher deformability index (DI) (9.62 ± 0.15 g) compared to traditional niosomal formulation (0.92 ± 0.12 g). Further, N15 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis-(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition tests revealed a superior TCZ deposition inside the skin from N15 in comparison to traditional niosomal formulation and TCZ suspension. Furthermore, histopathological examination for rats assured the safety of N15 for topical use. A clinical study conducted on infants suffering from napkin candidiasis proved the superiority of N15 to placebo in providing a complete cure of such fungal infections. CONCLUSION: Concisely, the obtained outcomes confirmed the pronounced efficacy of N15 to successfully treat skin fungal infections.