An in vitro study for reducing the cytotoxicity and dose dumping risk of remdesivir via entrapment in nanostructured lipid carriers.

The aim of this study was to synthesize and evaluate nanostructured lipid carriers (NLCs) loaded with Remdesivir (RDV) to control its side effects in COVID-19 patients. Due to the low solubility and short half-life of RDV in the blood, an injectable formulation was prepared using sulphobutylether-beta-cyclodextrin. However, it can accumulate in the kidney and cause renal impairment. NLCs improve the parenteral delivery of hydrophobic drugs such as RDV by increasing drug solubility and bioavailability. For the synthesis of RDV-NLCs, the aqueous phase containing Tween 80 was injected into the lipid phase under rapid stirring and was sonicated. The experimental conditions were optimized using Box-Behnken design and Design Expert software. The optimum formulation contained a total lipid of 2.13%, a total surfactant of 1%, and a hot bath time of 71 min. The optimum formulation showed particle size, polydispersity index, zeta potential, and entrapment efficiency values of 151.0 ± 1.7 nm (from 149.1 to 152.1), 0.4 ± 0.1 (from 0.3 to 0.5), -43.8 ± 1.2 mV (from -42.4 to -44.7), and 81.34 ± 1.57% (from 79.52 to 82.33%), respectively. RDV-NLCs showed acceptable stability for 30 days at 25 â„ƒ and were compatible with commonly used intravenous infusion fluids for 48 h. FE-SEM images of RDV-NLC showed spherical particles with a mean diameter of 207 nm. The NLC-RDV formulation showed a sustained release of RDV with a low risk of dose-dumping, minimizing potential side effects. In addition, RDV in the form of RDV-NLC causes less cytotoxicity to healthy normal kidney cells, which is expected to reduce renal impairment in COVID-19 patients.

C. difficile biomarkers, pathogenicity and detection.

BACKGROUND: Clostridioides difficile infection (CDI) is the main etiologic agent of antibiotic-associated diarrhea. CDI contributes to gut inflammation and can lead to disruption of the intestinal epithelial barrier. Recently, the rate of CDI cases has been increased. Thus, early diagnosis of C. difficile is critical for controlling the infection and guiding efficacious therapy. APPROACH: A search strategy was set up using the terms C. difficile biomarkers and diagnosis. The found references were classified into two general categories; conventional and advanced methods. RESULTS: The pathogenicity and biomarkers of C. difficile, and the collection manners for CDI-suspected specimens were briefly explained. Then, the conventional CDI diagnostic methods were subtly compared in terms of duration, level of difficulty, sensitivity, advantages, and disadvantages. Thereafter, an extensive review of the various newly proposed techniques available for CDI detection was conducted including nucleic acid isothermal amplification-based methods, biosensors, and gene/single-molecule microarrays. Also, the detection mechanisms, pros and cons of these methods were highlighted and compared with each other. In addition, approximately complete information on FDA-approved platforms for CDI diagnosis was collected. CONCLUSION: To overcome the deficiencies of conventional methods, the potential of advanced methods for C. difficile diagnosis, their direction, perspective, and challenges ahead were discussed.