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, (Y₁) and the total amount of erythromycin that penetrated the skin after 6 h, Q6h (Y₂), 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 (µg/cm²) 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 μg/cm²·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.

Ginger, a natural plant belonging to the Zingeberaceae family, has been reported to have reasonable anti-inflammatory effects. The current study aimed to examine ginger extract transdermal delivery by generating niosomal vesicles as a promising nano-carrier incorporated into emulgel prepared with sesame oil. Particle size, viscosity, in vitro release, and ex vivo drug penetration experiments were performed on the produced formulations (ginger extract loaded gel, ginger extract loaded emulgel, ginger extract niosomal gel, and ginger extract niosomal emulgel). Carrageenan-induced edema in rat hind paw was employed to estimate the in vivo anti-inflammatory activity. The generated ginger extract formulations showed good viscosity and particle size. The in vitro release of ginger extract from niosomal formulation surpassed other formulations. In addition, the niosomal emulgel formulation showed improved transdermal flux and increased drug permeability through rabbit skin compared to other preparations. Most importantly, carrageenan-induced rat hind paw edema test confirmed the potential anti-inflammatory efficacy of ginger extract niosomal emulgel, compared to other formulations, as manifested by a significant decrease in paw edema with a superior edema inhibition potency. Overall, our findings suggest that incorporating a niosomal formulation within sesame oil-based emulgel might represent a plausible strategy for effective transdermal delivery of anti-inflammatory drugs like ginger extract.

Background/Objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB’s low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB’s bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects. Methods: Numerous S-INV formulations were developed using Box–Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan. Results: Phospholipids (1.72% w/w), cholesterol (0.15% w/w), ethanol (1% v/v), and cineole (1.5% v/v) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity. Conclusions: These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC.