ABSTRACT
The present investigation was aimed to synthesize, optimize, and characterize lipid/drug conjugate nanoparticles for delivering 5-fluorouracil (5-FU) to treat brain cancer. The Box-Behnken design was used to optimize the formulation, evaluate the particle size, entrapment efficiency, morphology, in vitro drug release study, and stability profiles. The in vitro performance was executed using cell line studies. The in vivo performance was carried out for pharmacokinetic studies, sterility test, biodistribution studies, and distribution lipid-drug conjugated (LDC) nanoparticles in the brain. Particle size, zeta potential, entrapment efficiency, and morphology of the optimized formulation demonstrated desirable results. In vitro release pattern showed initial fast release, followed by sustained release up to 48 h. Cytotoxic effects of blank stearic acid nanoparticles, LDC nanoparticles, and 5-FU solution on human glioma cell lines U373 MG cell showed more cytotoxicity by LDC-NPs compared to others. The values reported for LDC (AUC = 19.37 ± 0.09 µg/mL h and VD 2.4 ± 0.24 mL) and pure drug (AUC = 8.37 ± 0.04 µg/mL h and VD = 5.24 ± 0.29 mL) indicate higher concentrations of LDC in systemic circulation, while pure 5-FU was found to be largely available in tissue rather than blood circulation. The t1/2 for LDC represents an approximate rise by ninefold, while MRT (12.10 ± 0.44 h) denotes 12-fold rise than pure 5-FU indicating the prolonged circulation of LDC. Free 5-FU concentration in the brain was maximum (5.24 ± 0.01 µg/g) after 3 h, while for the optimized formulation of LDC it was twofold greater estimated as 11.52 ± 0.32 µg/g. In conclusion, the efficiency of 5-FU to treat the brain is increased when it is formulated with LDC nanoparticles.
ABSTRACT
Diabetes is one of the most common disorders that substantially contributes to an increase in global health burden. As a metabolic disorder, diabetes is associated with various medical conditions and diseases such as obesity, hypertension, cardiovascular diseases, and atherosclerosis. In this review, we cover the scientific studies on sodium/glucose cotransporter (SGLT) inhibitors published during the last decade. Our focus on providing an exhaustive overview of SGLT inhibitors enabled us to present their chemical classification for the first time.
ABSTRACT
Combined nano zinc oxide and titanium dioxide [nano (ZnO-TiO(2))] has been reported first time for the synthesis of novel series of 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine. All the synthesized compounds (7a-7m) are novel and were screened for their antimicrobial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis and antifungal activity was determined against two strains Candida albicans and Aspergillus niger. SAR for the newly synthesised derivatives has been developed by comparing their MIC values with ampicillin, ciprofloxacin and miconazole for antibacterial and antifungal activities, respectively. Among the synthesized compounds, 2,6 dichlorophenyl analogue (7f), 4 fluorophenyl analogue (7k) and 2,6 dichlorophenyl analogue (7l) shows promising antibacterial as well as antifungal activity whereas thiophene substituted compound (7j) shows promising antibacterial activity.
