الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
FU entrapment efficiency decreased only slightly upon the addition of various concentrations of sodium chloride to 5-FU/CTAB-GNPs, 5- FU/PEI-GNPs and 5-FU/BC-GNPs, but there was a general decrease in the intensity of GNPs characteristic surface plasmon resonance (SPR) peaks and red shift upon increasing sodium chloride concentration. 3. There was a significant increase in GNPs size with increasing 5-FU/BC, 5-FU/CTAB and 5-FU/PEI molar ratios (p<0.05). Most of 5-FU/BC-GNPs, 5-FU/PEI-GNPs and 5-FU/CTAB-GNPs had a polydispersity index ≤0.3 indicating their acceptable monodispersity. 4. TEM images revealed that nanoparticles were uniform in appearance and spherical in shape. 5. GNPs stored for 6 months showed excellent stability. There was no significant change (p>0.05) in zeta potential and drug entrapment efficiency (%) for GNPs stored at 4°C and at room temperature. 6. Slower 5-FU release was observed for all GNPs formulations, drug release rate from 5-FU/BC-GNPs and 5-FU/CTAB-GNPs was significantly slower than that from 5-FU/PEI-GNPs at all studied pH values (p<0.05). 7. Better anticancer effect against colon cancer cells was observed for 5- FU/CTAB-GNPs compared with free drug. Also, 5-FU/CTAB-GNPs were significantly more effective than 5-FU/GSH-GNPs (p<0.05) against colon cancer cells. For instance, cell treatment with 5-FU/CTAB-GNPs at concentration of 1.5 mg/mL resulted in late apoptotic and dead cells percent of 91.66±6.37% compared to 77.7 ±6.49% for cells treated with 5-FU/GSH-GNPs as the same drug concentration. 8. 5-FU/CTAB, 5-FU/BC and 5-FU/PEI complexes had significantly higher skin permeation when compared with free 5-FU solution (p<0.01). 5-FU/CTAB-GNPs, 5-FU/BC-GNPs and 5-FU/PEI-GNPs had even significantly higher drug permeability (p<0.01) through the skin compared with 5-FU/CTAB, 5-FU/BC complex, 5-FU/PEI complex and free 5-FU solution. III-Preparation and in vivo evaluation of 5-FU GNPs gel and cream formulations The work in this section included the following: 1. Preparation of 5-FU-GNPs topical preparations using 5-FU/CTABGNPs (5-FU: CTAB molar ratio of 1:1) equivalent to 1% w/w drug 1.incorporated into different gel and cream bases. 2. characterization of GNPs gel and cream preparations that included, the determination of their viscosity and in vitro drug release profiles. 3. Ex vivo skin permeability studies which include determination of flux (Jss), apparent permeability coefficient (Papp) and the enhancement factor (EF) for GNPs-formulations. 4. Monitoring of tumor growth for mice treated with 5-FU-GNPs gel or cream. The mice were previously injected S.C. with A431 skin cancer cell. Tumor tissues were examined histologically after staining using hematoxylin–eosin (H & E). The results of this section revealed that: 1. Slower release was observed for 5-FU/CTAB-GNPs cream and gel compared with free 5-FU gel and cream at pH 7.4 with drug release being predominately reflective of the viscosity of the gel and cream formulations. 2. 5-FU/CTAB-GNPs incorporated into gel and cream formulations had significantly higher skin permeation (p<0.01) compared with free 5-FU gel and cream. 3. Treatment with the 5-FU/GNPs cream or gel was significantly more effective (p<0.01) in inhibiting the tumor growth compared with free 5-FU preparations. The weights of untreated mice or that treated with free 5-FU gel and cream were significantly (p<0.05) lower than that in mice treated with 5-FU GNPs cream and gel. Examination of tumor tissues microscopically revealed near total regression of the infiltrating malignant cells in mice treated with 5-FU/GNPs formulations. Taken together, the aforementioned results confirm that GNPs could be used as effective delivery systems to enhance 5-FU anticancer efficacy against colorectal and skin cancers.