Abstract
Erythromycin (EM) is a macrolide antibiotic that is frequently used to treat skin bacterial infections. It has a short half-life (1-1.5 h), instability in stomach pH, and a low oral bioavailability. These foregoing factors limit its oral application; therefore, the development of topical formulations loaded with erythromycin is an essential point to maximize the drug's concentration at the skin. Accordingly, the current study's goal was to boost the antimicrobial activity of EM by utilizing the advantages of natural oils such as cinnamon oil. Erythromycin-loaded transethosomes (EM-TE) were generated and optimized using a Box-Behnken design employing, phospholipid concentration (A), surfactant concentration (B), and ethanol content (C) as independent variables. Their effects on entrapment efficiency, EE, (Y-1) and the total amount of erythromycin that penetrated the skin after 6 h, Q6h (Y-2), were assessed. The optimized transethosome showed a particle size of 256.2 nm, EE of 67.96 +/- 0.59%, and Q6h of 665.96 +/- 5.87 (mu g/cm(2)) after 6 h. The TEM analysis revealed that, the vesicles are well-known packed structures with a spherical shape. The optimized transethosomes formulation was further transformed into a cinnamon oil-based emulgel system using HPMC as a gelling agent. The generated EM-TE-emulgel was characterized by its physical features, in vitro, ex vivo studies, and antimicrobial activities. The formulation showed sufficient characteristics for effective topical application, and demonstrated a great stability. Additionally, EM-TE-Emulgel had the highest transdermal flux (120.19 mu g/cm(2)center dot h), and showed considerably (p < 0.05) greater antimicrobial activity, than EM-TE-gel and placebo TE-Emulgel. The action of EM was subsequently augmented with cinnamon oil, which eventually showed a notable effect against bacterial growth. Finally, these results demonstrate that the transethosomes-loaded cinnamon oil-based emulgel is an alternative way to deliver erythromycin for the treatment of topical bacterial infections.