<p>Novel Approach for Transdermal Delivery of Rifampicin to Induce Synergistic Antimycobacterial Effects Against Cutaneous and Systemic Tuberculosis Using a Cationic Nanoemulsion Gel</p>

Abstract

This study demonstrated improved transdermal delivery of rifampicin-loaded cationic nanoemulsion gel to treat systemic and cutaneous tuberculosis using capmul, labrasol, and acconon, which exert anti-Mycobacterium activities. This approach enhanced drug permeation across the skin, increased therapeutic efficacy, and reduced dose-related side effects. Methods: Design Expert ® was used to optimize formulations (S mix ratio and capmul as independent factors), which were prepared using a slow spontaneous titration method. The optimized nanoemulsion was incorporated into carbopol gel to allow for topical application and comparative assessments. Nanoemulsions and gels were evaluated for size, size distribution, shape, zeta potential, percent spread, viscosity, in vitro hemolysis, in vitro release, and ex vivo skin permeation and deposition. A mechanistic evaluation was performed using scanning electron microscopy. Furthermore, in vivo pharmacokinetic and irritation studies were performed. Results: The optimized cationic nanoemulsion (OCNE-1) was characterized by small particle size (≤100 nm), had optimal viscosity, percent spread, zeta potential, and percent drug release, and was hemocompatible. The OCNE-1T gel exhibited higher permeation flux (51.32 ± 0.5 µg/cm 2 hr), permeation coefficient (2.566 ± 0.08 cm/hr), drug deposition (994.404 µg/cm 2), and enhancement ratio (7.16) than those of the OCNE-1 nanoemulsion or drug solution. Scanning electron microscopy was used to characterize the mechanism of enhanced permeation. An In vivo study showed that the C max and area under the curve following transdermal application were 4.34-and 4.74-fold higher than those following oral administration. Conclusion: Transdermal delivery of rifampicin could be a promising alternative to conventional approaches to treat systemic and local tuberculosis, and other bacterial infections.

Application of Green Nanoemulsion for Elimination of Rifampicin from a Bulk Aqueous Solution

“…Rifampicin was assayed using a previously established method [ 25 ]. The drug content was estimated using a RP-C 18 column (150 × 4.6 mm, 5 μm, Purospher Star, Merck, Germany).…”

“…RIF is poorly soluble in water (~1–2 mg/mL) at 25 °C, whereas it is soluble in CMC8, DMSOT, and isopropyl alcohol [ 24 , 25 ]. Therefore, we added DMSOT (5% v / v ) in an aqueous medium for stock solution.…”

“…Rifampicin (RIF) is the most clinically effective and established first-line anti-tubercular drug. The drug (molecular weight = 822.94 g·mol −1 ) is highly crystalline and hydrophobic (log P = 3.8) with limited aqueous solubility (~1–2 mg/mL soluble in water) [ 24 , 25 ]. The drug is associated with peripheral neuropathic toxicity, chemical instability in the stomach (~32% as desacetylrifampicin), and limited oral absorption [ 26 , 27 , 28 ].…”

<p>Development and Characterization of A New Dimethicone Nanoemulsion and its Application for Electronic Gastroscopy Examination</p>

“…The titration phenomenon presented started turbid to clear, and ended clear to turbid. 25 However, a few research papers showed a point, not a region in the procedure of their pseudo-ternary phase diagrams construction, 26,[39][40][41][42] this question needs to be deliberated. Figure 3 exhibited the picture taken under optical microscope, DMNs dyed with methylene blue and the droplet was colored blue on the outside.…”

“…So it is theoretically speculated that the DMNs should be relatively safe and non-toxic. But the body processes, absorption sites, 42,45 as well as long-term toxicity of DMNs, have not been performed. Third, during the gastroscopy to observe the effect of the drug, administered via the tube injection method 13 (the insertion of a plastic tube through a gastroscopy biopsy hole) is a reliable scheme to evaluate the effect of drug, which can be used to show the contrast before and after administration.…”