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.