The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans.

Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by Candida albicans treatment's efficacy. This study aimed to develop ureasil-polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 µg/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 µg/mL, while that of CUR decreased eight-fold to 32 µg/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO/MCZ and U-PEO/CUR/MCZ ovules showed the greatest zones of inhibition (≥18 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.

Potential Application of Cephalosporins Carried in Organic or Inorganic Nanosystems against Gram-Negative Pathogens.

Cephalosporins are ß-lactam antibiotics, classified into five generations and extensively used in clinical practice against infections caused by Gram-negative pathogens, including Enterobacteriaceae and P. aeruginosa. Commercially, conventional pharmaceutical forms require high doses to ensure clinical efficacy. Additionally, ß-lactam resistance mechanisms, such as the production of enzymes (called extended-spectrum ß-lactamases) and the low plasma half-life of these antibiotics, have been challenging in clinical therapy based on the use of cephalosporins. In this context, its incorporation into nanoparticles, whether organic or inorganic, is an alternative to temporally and spatially control the drug release and improve its pharmacokinetic and pharmacodynamic limitations. Considering this, the present review unites the cephalosporins encapsulated into organic and inorganic nanoparticles against resistant and nonresistant enterobacteria. We divide cephalosporin generation into subtopics in which we discuss all molecules approved by regulatory agencies. In addition, changes in the side chains at positions R1 and R2 of the central structure of cephalosporins for all semisynthetic derivatives developed were discussed and presented, as the changes in these groups are related to modifications in pharmacological and pharmacokinetic properties, respectively. Ultimately, we exhibit the advances and differences in the release profile and in vitro activity of cephalosporins incorporated in different nanoparticles.