RESUMO
The present research was aimed to develop a terbinafin hydrochloride (TH)-encapsulated solid lipid nanoparticles (SLNs) hydrogel for improved antifungal efficacy. TH-loaded SLNs were obtained from glyceryl monostearate (lipid) and Pluronic® F68 (surfactant) employing high-pressure homogenization. The ratio of drug with respect to lipid was optimized, considering factors such as desired particle size and highest percent encapsulation efficiency. Lyophilized SLNs were then incorporated in the hydrogel prepared from 0.2-1.0% w/v carbopol 934P and further evaluated for rheological parameters. The z-average, zeta potential and polydispersity index were found to be 241.3 nm, -15.2 mV and 0.415, respectively. The SLNs show a higher entrapment efficiency of about 98.36%, with 2.12 to 6.3602% drug loading. SEM images, XRD and the results of the DSC, FTIR show successful preparation of SLNs after freeze drying. The TH-loaded SLNs hydrogel showed sustained drug release (95.47 ± 1.45%) over a period of 24 h. The results reported in this study show a significant effect on the zone of inhibition than the marketed formulation and pure drug in Candida albicans cultures, with better physical stability at cooler temperatures. It helped to enhance skin deposition inthe ex vivostudy and improved, in vitro and in vivo, the antifungal activity.
RESUMO
A series of 3-{2-[1-acetyl-5-(substitutedphenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-ones 24-43 was synthesized using an appropriate synthetic route and evaluated experimentally by the maximal electroshock test. These compounds were evaluated for antidepressant and antianxiety activities. The most active compound, 3-{2-[1-acetyl-5-(4-chlorophenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-one 25, exhibited an ED50 of 13.19 mmol/kg, a TD50 of 43.49 mmol/kg, and a high protective index of 3.29, compared with the standard drug diazepam. To get insights into the intermolecular interactions, molecular docking studies were performed at the active site of the GABAA receptor and the MAO-A enzyme. Molecular docking studies are also in agreement with the pharmacological evaluation with potent compounds, exhibiting docking scores of -1.5180 and 0.7458 for the GABAA receptor and MAO-A, respectively. The 3D-QSAR analysis was carried out by Vlife MDS engine 4.3.1, and a statistically reliable model with good predictive power (r2 = 0.7523, q2 = 0.3773) was achieved. The 3D-QSAR plots gave insights into the structure-activity relationship of these compounds, which may aid in the design of potent benzopyrrole derivatives as anticonvulsant agents. So, our research can make a great impact on those medicinal chemists who work on the development of anticonvulsant agents.
