Development and evaluation of surfactant-based elastic vesicular system for transdermal drug delivery / Asmaa Ashraf Mohamed Nemr; Supervised Galal Elmahrouk , Hany Abo Badie

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Peripheral arterial disease (PAD) is the most prevalent manifestations of systemic atherosclerosis, affecting more than 200 million individuals globally with high morbidity and mortality. Intermittent claudication (IC) is the most common and early symptom in patients with PAD. It is an aching pain in one or both legs that occurs during walking or exercise and relieved only by rest. About one-third of patients with PAD have a typical IC.The disease progression increased slowly in patients with IC. However, almost all patients with PAD exhibit a reduced functional capacity that limits their ability to perform daily activities.For the treatment of IC, many drugs have been tested with disappointing results such as prostaglandins, antiplatelet medications, serotonin blockers, and vasodilators. But none have exhibited significant benefits on patients with IC. Only two drugs approved by the FDA for the treatment of IC (Cilostazol and Pentoxifylline). Pentoxifylline (Trental) acts by decreasing the "stickiness" (viscosity) of blood and thereby improves its flow through arteries. But, Cilostazol (CLZ) only has demonstrated consistent efficacy in both extending exercise capacity and improving quality of life. CLZ, a type III phosphodiesterase enzyme (PDE) inhibitor, a potent inhibitor of platelet aggregation with vasodilating properties, selectively inhibits cyclic adenosine monophosphate (cAMP){u2013}selective phosphodiesterase, thereby increasing the intracellular level of (cAMP) by blocking its hydrolysis.CLZ undergoes extensive first-pass metabolism by cytochrome P-450 enzyme and is associated with oral side effects like headache, abdominal pain, diarrhea, abnormal stool, nausea and gastrointestinal hemorrhage.In addition, the oral bioavailability of CLZ is affected by food as high fat meals increase the absorption and bioavailability of CLZ and may cause toxicity

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