الفهرس 
General introductionOnly 14 pages are availabe for public view
Abstract
Silymarin, a polyphenolic substance extracted from milk thistle, is a mixture of four isomeric flavonolignans: silibinin, isosilibinin, silydianin and silychristin. It has an optimistic influence on physiology of liver cells as a unique hepatoprotective agent through capturing of free radical and inhibiting peroxidation of lipids.
However, its effectiveness as hepatoprotective is narrowed by its low water solubility and reduced bioavailability after oral administration of 800 mg/day in two or three divided dose(128, 129)due to extensive metabolism and rapid excretion along with low permeability through intestinal epithelial cells. The high incidence of administration of silymarin together with its short t1/2 and poor bioavailability proposed great scope for the proposal of nanoparticulate drug delivery systems. Polymeric NPs are a promising vehicle from the pharmaceutical point of view.
A variety of polymers could be utilized among which Eudragit polymers which have numerous advantages including, positive surface charge, modest bioadhesive force, as well as absence of possible irritant effect on mucosa. The objectives of the thesis were to: 1. Formulate and characterize silymarin loaded Eudragit nanoparticles (SNPs) in an attempt to improve release and permeation properties and, consequently, its bioavailability.
2. Evaluate the hepatoprotective and cytotoxic effects of the prepared silymarin loaded Eudragit nanoparticles (SNPs). The work was divided into three chapters:
Chapter 1: Preparation and physicochemical characterization of silymarin loaded Eudragit nanoparticles (SNPs). Eudragit loaded SNPs were successfully prepared using nanoprecipitation technique. Preliminary studies were performed to select the most appropriate method of preparation and to select the optimum drug to polymer ratio based on the NPs particle size (PS) and PDI. Stirring of the organic phase with the aqueous phase on a magnetic stirrer for 5 min followed by homogenization at 23.000 krpm for 30 min was the selected method for NPs formation along with drug: polymer ratio 1:1 w/w. Three different organic to aqueous phase ratios were used 1:6, 1:10 and 1:20 v/v along with different PVA concentrations (1, 2 and 3%). The main criteria for selecting the optimum SNP were PS, PDI, entrapment efficiency and % drug release. The formulation coded as N3 of particle size of 84.70 nm ± 2.032 and entrapment efficiency of 83.45% ± 2.16 with 100% drug release after 12 h was selected as optimum formulation. TEM revealed that most of the nanoparticles were spherical in shape and uniformly distributed. DSC study suggested the presence of silymarin in an amorphous state that could account for the enhanced dissolution of silymarin.
FT-IR study revealed the absence of chemical interaction during the nanoparticles formation.