الفهرس 
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Abstract
The design and development of a new drug delivery system with a view to enhance the efficacy of existing drugs is an ongoing process in the pharmaceutical research. br Such delivery systems include solid lipid nanoparticles (SLN), liposomes, niosomes, polymeric nanoparticles, microparticles and many others. These delivery systems are considered to be promising systems considering drug targeting to specific sites, maximizing the therapeutic effect of some drugs and minimizing their side effects. br SLNs are colloidal lipid particles made of solid lipid materials that are stabilized by different types of surfactants and co-surfactants. They are used to deliver drugs via parenteral, ophthalmic and topical routes. They are used mainly in topical preparations as they are composed of non-irritant and non-toxic materials. They have an occlusive effect on the skin by decreasing water loss and hence increasing drug penetration through the stratum corneum. br Non-ionic surfactant based vesicles (niosomes) are formed -#102;-#114;-#111;-#109; hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids. They are usually used to incorporate hy-#68;-#82;-#79;-#80;hilic drugs within their core; however hy-#68;-#82;-#79;-#80;hobic drugs can be incorporated into niosomes lipophilic membrane. br Chemotherapeutic agents are cytotoxic drugs that are used to treat cancer because they are toxic to cancer cells that are characterized by rapid division and growth. These agents however are known for their profoundly toxic side effects because of which treatment failure still frequently encountered. br 5-Fluorouracil (5-FU or 5-fluoro-2,4-pyrimidinedione) is one of the chemotherapeutic agents which is characterized by its activity against solid tumors like breast cancer, colon cancer and skin tumors. Nevertheless, 5-FU has many disadvantages including development of resistance to it by cancer cells and high rate of metabolism which leads to requirement of high doses of 5-FU in -#111;-#114;-#100;-#101;-#114; to keep its therapeutic serum concentration leading to sever side effects. The mentioned points make 5-FU a good candidate for loading on drug delivery systems which can accumulate such a drug in the requited action site leading to improvement in its therapeutic action and decreasing its serious side effects. br The work in this thesis is divided into br • Chapter I: Formulation and evaluation of 5-flourouracil loaded solid lipid nanoparticles br br This chapter includes the preparation and characterization of 5-FU loaded SLN. Also the in vitro release and permeation studies of the prepared SLNs were performed. br In this chapter physicochemical properties of 5-FU (spectrophotometric scanning and saturated solubility in Sӧrensen’s Phosphate Buffer (pH 5.5) and Phosphate Buffer Saline (pH 7.4)) were first evaluated. br Pre-formulation study was carried out to detect interaction between 5-FU and SLNs’ components using Differential Scanning Colarimetry (DSC) and Fourier-transform Infrared spectroscopy (FT-IR). br SLNs preparation experiment was designed using 32 factorial design. SLNs formulae were prepared using stearic acid, different percentages of lecithin and different percentages of poloxamer188 using modified solvent diffusion-evaporation method. The concentration of 5-FU in each formula was 10 mg. br The prepared formulae were characterized with respect to encapsulation efficiency, particle size measurement by photo correlation spectroscopy (PCS), zeta potential, Transmission electron microscopy (TEM), scanning electron microscopy (SEM), in vitro permeation study and in vitro release study. br In vitro permeation study through lipophilic membrane was performed using double open-sided tube with diffusion area of 5 cm2 and 25 ml receptor medium. The contents of the donor compartment (SLNs) and receptor compartment (PBS (ph 7.4)) were separated using cellulose nitrate membrane of pore size 0.2 µm which was immersed in isopropyl myristate to simulate the lipophilic properties of stratum corneum. The receptor compartment was maintained at 37±0.5 oC while the donor compartment was left exposed to ambient temperature. The donor compartment’s solution was stirred at 100 r.p.m by means of magnetic stirrer. Samples were withdrawn at specific time intervals and analyzed spectrophotometrically at 266 nm. The permeation parameters of different SLNs formulae along with plain drug were calculated. br Release experiments were carried out on SLNs formulae using reported method with modification. Certain volume of SLNs was inserted in dialysis bags that were then attached to the paddles of USP dissolution tester (apparatus II). The temperature of the medium (Sӧrensen’s Phosphate Buffer (pH 5.5)) was set at 32±0.5oC and speed of rotation was set at 50 r.p.m. samples were withdrawn at certain time intervals and diluted and the medium was compensated with equal volume of fresh medium. The linear regression analysis was applied to all in-vitro release results. The correlation coefficient (r2) was determined in each case and accordingly, the -#111;-#114;-#100;-#101;-#114;s of dissolution were determined.