Due to the increased emergence of drug-resistant bacteria, the declining efficiency of traditional antimicrobials has generated severe concerns in recent years. Subsequently, more interest in other antimicrobial agents from natural resources draws more attention as an alternative to conventional medications. This study investigated the bactericidal mechanism of monoterpene 1,8-cineol (eucalyptol), a major compound of various essential oils, against methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial activity of 1,8-cineol was assessed by an MTT assay against clinical and reference MRSA strains. A cell membrane integrity test, followed by zeta potential (ZP) measurements, was performed to evaluate the disruption of the bacterial membrane integrity. Additionally, the cytotoxic effect of this molecule on MRSA bacteria was investigated by monitoring reactive oxygen species (ROS) generation, lipid peroxidation (MDA), and antioxidant enzyme activities (CAT and SOD). Regarding the anti-staphylococcal effect, the obtained results revealed the antibacterial efficacy of 1,8-cineol wherein the minimum inhibitory concentrations were equal to 7.23 mg/mL. Furthermore, it enhanced membrane permeability, with a 5.36-fold increase in nucleic acid and protein leakage as compared with untreated strains, along with the alteration of surface charge (ZP) in MRSA cells. The tested compound caused an increase in ROS generation reaching 17,462 FU and MDA production, reaching 9.56 μM/mg protein, in treated bacterial cells, along with a decrease in oxidative stress enzymes activities. Our findings suggest that 1,8-cineol has the ability to damage the membrane integrity and induce ROS-mediated oxidative stress in MRSA cells, leading to its antagonistic effect against this pathogen and consequently aiding in the reversal of antibiotic resistance.

The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) as to improve the transcorneal permeability of voriconazole. A “mixture design around a reference mixture” approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween® 80 and Span^® 80 as oil, co-solvent, surfactant and co-surfactant,respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. Ex-vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement (p < 0.05) in apparent permeability coefficient (1.982 ± 0.187x10⁻⁶ cm/s) when compared to commercialized formulation (1.165 ± 0.106x10⁻⁶ cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.

This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its application as a topical treatment for psoriasis. Solubility studies were conducted to select the oil, surfactant, and co-surfactant. Phase diagrams were constructed using the aqueous phase titration method. All the formulations were in nanoscale, and Formula (F2) (which contains oleic acid oil as the oil phase, a mixture of Surfactant Tween 80 and co-surfactant (ethanol) at a ratio of 1:2 in addition to distilled water as an aqueous phase in a ratio of 1:5:4, respectively) was the selected formula depending on the particle size, PDI, and zeta potential. Formula (F2) has the best ratio because it gives the smallest nanoemulsion globule size (particle size average of 167.1 nm), the best homogenicity (lowest PDI of 0.195), and the highest stability (higher zeta potential of −32.22). The selected formula was converted into a nanoemulgel by the addition of 0.5% (w/w) xanthan gum (average particle size of 172.7 nm) and the best homogenicity (lowest PDI of 0.121%) and highest stability (higher zeta potential of −28.31). In conclusion, the selected formula has accepted physical and chemical properties, which enhanced skin penetration.

– Purpose. Oral drug administration remains the most common and most convenient way used in clinical therapy. The availability of a simple, rapid, economic and reproducible in vitro method to assess drug absorption is a very helpful tool. The purpose of this study is to compare the performance of Sartorius SM 16750 Absorption Simulator apparatus to Everted Gut Sac (EGS) technique in terms of predicting drug absorption. Methods. Permeation studies across these two in vitro models were performed with six drugs selected across the Biopharmaceutics Classification System (BCS) categories: Tramadol (class I of BCS), doxcycycline (class I of BCS), diclofenac (class II of BCS), clopidogrel (class II of BCS), metformin (class III of BCS) and chlorothiazide (class IV of BCS). Results. Apparent permeability coefficient (Papp) and diffusion profiles obtained with EGS and Sartorius SM 16750 apparatus were similar for diclofenac and metformine. But there were differences in results, for the other molecules. Conclusion. It could be concluded that the Sartorius SM 16750 apparatus, easier to carry out, could be an alternative to EGS when drug passage across intestinal barrier occurs by passive diffusion and when no efflux system is implicated in limiting the transepithelial passage.