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Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3(2) factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67 nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32-33 °C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n = 0.582) and G6 (n = 0.648) showed Korsemeyer-Peppas (KKP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9 µg/cm(2) for G3 and G6, respectively, revealed very little difference in release rate after 24 h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.

The leaves and bark of Cassia glauca Lam., a glabrous tree in the family Fabaceae, are used in folk medicine for the treatment of diabetes. The aim of this study was to investigate the antidiabetic activity of the aqueous extract of C. glauca bark. The various parameters that were studied in treated or untreated normoglycemic and STZ-induced diabetic rats included the effect of the aqueous extract on oral glucose tolerance, fasting blood glucose, body weight, serum lipids, liver glycogen, serum insulin, and glycosylated haemoglobin. Oral administration of the aqueous extract of C. glauca bark at a dose of 500 mg/kg significantly reduced the effect of external glucose load. In a chronic treatment model, aqueous extract and glibenclamide (0.25 mg/kg) were administered for 21 days. At the end of the treatment, there was a significant increase in liver glycogen, serum insulin, and HDL cholesterol for both treatments. A significant decrease in fasting blood glucose, glycosylated haemoglobin, total cholesterol, and serum triglycerides was also observed. The body weights of the animals were observed to be consistent throughout the study. The findings showed the significant antidiabetic potential of the extract in ameliorating the diabetic condition in the diabetic rats. No significant activity was found in the normoglycemic rats.

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