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

Authors Hussain A, Altamimi MA, Alshehri S, Imam SS, Shakeel F, Singh SK

Received 27 October 2019

Accepted for publication 14 December 2019

Published 14 February 2020 Volume 2020:15 Pages 1073—1094


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster

Afzal Hussain,1 Mohammad A Altamimi,1 Sultan Alshehri,1 Syed Sarim Imam,1 Faiyaz Shakeel,1 Sandeep Kumar Singh2

1Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Pharmaceutical Sciences, Birla Institute of Technology, Ranchi, Jharkhand, India

Correspondence: Afzal Hussain
Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia
Tel +966 5 64591584

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.

Keywords: systemic and cutaneous tuberculosis, nanoemulsion gel, transdermal delivery, permeation parameters, bioavailability

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