الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
Skin cancer represents the most widely recognized type of cancer among all the recorded malignancies. Seeking alternative therapies using safe nutraceuticals, such as EGCG is desirable in order to overcome the drawbacks that might exist upon using conventional skin cancer treatment options. However, its application in topical formulations has been problematic owing to its chemical instability and low bioavailability that result in inefficient delivery.
Therefore, this study aimed at EGCG encapsulation in different ultradeformable vesicular systems (UDVs) for topical administration that can offer a good solution for the numerous EGCG problems associated with the use of free EGCG. Moreover, the topical administration would ensure drug targeting to skin tumors which can further enhance its chemotherapeutic potential in the treatment of skin cancer. Optimized EGCG-loaded ultradeformable vesicular systems: penetration enhancer-containing vesicles (PEVs), ethosomes, transfersomes and transethosomes (TEs) were prepared in order to enhance the therapeutic efficacy of EGCG. A preliminary study was carried out for the optimization of the colloidal properties of the prepared vesicles (namely particle size, polydispersity index and zeta potential) through preparing empty vesicles. Further optimization trials were performed on EGCG-loaded vesicular systems through changing the volume of organic solvent and/or hydration medium in order to achieve high drug loading with good colloidal properties. The amount of phospholipid, penetration enhancers, drug and hydration medium affected the physicochemical properties of the vesicles.
Selected vesicular systems (EGCG-loaded PEVs, ethosomes and TEs) were characterized for viscosity, deformability, chemical compatibility, antioxidant properties, in-vitro release, ex-vivo skin deposition, photodegradation and physical stability after storage. The selected EGCG-loaded vesicular systems exhibited acceptable properties represented by reasonable skin deposition, retaining the inherent antioxidant properties of EGCG and good physical stability, except for EGCG-loaded ethosomes, that were excluded from further investigation as they displayed the lowest stability, represented by the highest increase in the vesicle size with significant drug leakage. EGCG-loaded PEVs and TEs selected for in-vitro and in-vivo investigations, proved the inhibitory effect of the vesicles on epidermoid carcinoma cell line (A431) in addition to reduced tumor sizes in mice, confirmed with histopathological analysis and biochemical quantification of skin oxidative stress biomarkers.
Therefore, the encapsulation of EGCG in penetration enhancer-containing vesicles succeeded in offering an effective delivery system targeting skin cancer, in an attempt to widen the scope of EGCG dermal delivery by rapidly crossing the stratum corneum and releasing the encapsulated drug at deeper skin layers. In addition, the optimized EGCG-loaded vesicular system protected the encapsulated drug against degradation, improving the antioxidant capacity and anticancer efficacy of EGCG.