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

Abstract

PURPOSE:

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 (Smix 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/cm2 hr), permeation coefficient (2.566 ± 0.08 cm/hr), drug deposition (994.404 µg/cm2), 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 Cmax 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.

• Authors: Afzal Hussain, Mohammad A Altamimi, Sultan Alshehri, Syed Sarim Imam, Faiyaz Shakeel, Sandeep Kumar Singh
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 15 Pg. 1073-1094 ( 2020) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 32103956 (Publication Type: Journal Article)
• Copyright: © 2020 Hussain et al.

Chemical References

• Acrylic Resins
• Antitubercular Agents
• Caprylates
• Cations
• Emulsions
• Excipients
• Gels
• Glycerides
• Labrasol
• carboxypolymethylene
• monooctanoin
• Rifampin

Topics

• Acrylic Resins (chemistry)
• Administration, Cutaneous
• Animals
• Antitubercular Agents (administration & dosage, pharmacokinetics, pharmacology)
• Biological Availability
• Caprylates (chemistry)
• Cations (chemistry)
• Emulsions (administration & dosage, pharmacology)
• Excipients (chemistry)
• Gels (chemistry, pharmacology)
• Glycerides (chemistry)
• Mycobacterium (drug effects)
• Nanostructures (administration & dosage, chemistry)
• Particle Size
• Rats, Sprague-Dawley
• Rifampin (administration & dosage, pharmacokinetics, pharmacology)
• Skin (drug effects)
• Tuberculosis (drug therapy)
• Tuberculosis, Cutaneous (drug therapy)