Development and evaluation of surfactant-based elastic vesicular system for transdermal delivery of Cilostazole: ex-vivo permeation and histopathological evaluation studies.

Cilostazole (CLZ) is an anti-platelet drug that suffers from extensive first pass-metabolism and gastrointestinal side effects. This study aimed to prepare spanlastics for enhancing the transdermal delivery of CLZ to avoid its oral problems. CLZ-loaded spanlastic dispersions were prepared by ethanol injection technique according to a 413121 full factorial design to investigate the effect of formulation variables on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and the percent of drug released after 2 and 24 h (Q2 and 24 h). Spanlastic-loaded gel of the optimized formula was prepared using hydroxypropyl methylcellulose (HPMC K4M). The optimum formula (F13), constitutes of Span60 and CremophoreRH40 at a weight ratio of 80:20 and distilled water for hydration, had the highest desirability value of (0.841) and exhibited the highest EE% of (69.29 ± 0.29%), PS of (452.7 ± 5.94 nm), ZP of (-32.6 ± 0.4 mV), Q 2 h of (33.28 ± 1.45%) and Q24h of (82.37 ± 1.37. F13 was subjected to ex-vivo permeation study and showed a cumulative amount permeated after 48 h(Q48h) equal to (750.71 ± 3 µg/cm2) in comparison to the drug suspension which showed Q48h equal to (190.20 ± 6.3 µg/cm2). Also, F13 showed an increase in the drug flux of (17.84 µg/cm2.h) and enhancement ratio(ER) of (5.71 ± 0.1) in comparison to the drug suspension that showed drug flux of (3.12 ± 0.0 µg/cm2.h). Spanlastics-loaded gel was subjected to an in-vitro release study compared to(F13) spanlastic dispersion and showed a more sustained release effect. In addition, histopathological studies showed no sign of skin alteration confirming safe delivery through the skin. CLZ showed promising results with high potential to be delivered transdermally.

Development and evaluation of proniosomes to enhance the transdermal delivery of cilostazole and to ensure the safety of its application.

Cilostazole (CLZ) is an anti-platelet drug that suffers from extensive first-pass metabolism and gastrointestinal side effects. This study aimed to prepare proniosomes for enhancing the transdermal delivery of CLZ to avoid its oral problems. proniosomes were prepared by a coacervation phase separation technique according to the D-optimal design to investigate the effect of formulation variables on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and the percent of the drug released after 2 and 24 h (Q2 and 24 h). The desirability criterion is set to select the optimum formula. The optimum formula(opt) with a desirability value (0.75), composed of 540 mg Span60 and 59.7 mg of cholesterol, had the highest EE% of (75.125 ± 0.125%), PS of (300.3 ± 0.2 nm), ZP of (-39.35 ± 0.15 mV), Q2h of (24.32 ± 0.13%) and Q24h of (81.175 ± 0.325%). Further, the opt-gel was prepared by using hydroxy propyl methyl cellulose (HPMC K4M). The opt-formula was subjected to an ex-vivo permeation study and showed a marked increase in drug flux of (22.89 ± 0.1 µg/cm2.h). The opt-gel was subjected to an in-vitro release study in comparison with the opt-formula that showed a more sustained release effect. The histopathological examination study confirmed the safety of the topical application of proniosomes. The CLZ-loaded proniosomes showed promising results with high potential to deliver it across the skin.

Effect of Cilostazol on the Ion Channel of Right Ventricular Cells in Experimental Rats / 中国循环杂志

Objective: To observe the effect of cilostazol on the ion channel of right ventricular cells in experimental rats, and to explore the ion channel mechanism of ciolstazol for preventing the ventricular arrhythmia in Brugada syndrome. Methods: Our research was composed of 2 groups: ①Perfusion group, the cells were treated in 4 sub-groups by cilostazole at 1, 2, 5, 50μmol/L respectively, and there were 9, 5, 3, 7 cells were recorded at each sub-group to observe the differences of current density Ito at before and after treatment. ②Oral group, which included 4 sub-groups:Control 1 with 7 rats, Experiment 1 with 5 rats, and Control 2 with 8 rats, Experiment 2 with 6 rats respectively. The differences of current density Ito and ICa,L were studied between each Control and Experiment sub-groups. Results: In Perfusion group,①with cilostazole 1, 2, 5, 50μmol/L treatment, the current density Ito decreased in all sub-groups, when the self-command voltage at+60mV, the Ito was signiifcantly different in each sub-group at before and after treatment, all P0.05. In Oral group,①When the self-command voltage from-50mV reached the maximum of+60mV, the Ito was similar between Control 1 and Experiment 1 sub-groups, P>0.05.②When the self-command voltage at+10mV, the current density of ICa,L was slightly higher in Control 2 sub-group than that in Experiment 2 sub-group, P>0.05. Conclusion: Direct perfusion of cilostazole in right ventricular cells may inhibit Ito in experimental rats, such effect was similar with cilostazole treatment at (1-50)μmol/L. Cilostazole might prevent the ventricular arrhythmia in Brugada syndrome in experimental rats.