الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Part I:
Development and appraisal of Genistein-Phospholipid complex formulations: An approach to improve oral bioavailability Different Gen-SPC complex formulations were prepared using different forms of soy phospholipid; solid form (Lipoid S 100), solubilized form with medium chain triglycerides (Phosal 53 MCT) and solubilized form with long chain triglycerides (Phosal 75 SA).
Results reveal a successful preparation of Gen phytosomes with mean particle size 150 nm and mean surface net charge -33.0 mV. TEM observations show formation of bilayer phospholipid vesicles upon dispersion in water for all Gen-SPC complex formulations. In-vitro lipolysis effect on Gen-SPC complex formulations followed by Ex-vivo permeation study was carried out to mimic the In-vivo conditions after oral administration.
Complete pharmacokinetics and tissue distribution studies were carried out in different tissue compartments (liver, IT, genital organs, lymph nodes, serum lipoprotein and blood). Effect of formulation on Gen metabolism was studied in different Gen-SPC complex formulations.
Results show high accumulation of Gen after oral administration of S-5 and SA-3 in liver while high accumulation of Gen was observed in genital organs after oral administration of preconcentrated MCT-3 and S-5. Hence S-5 and SA-3 formulations were subjected to subsequent study focuses on therapeutic activity of these formulations against hepatocellular carcinoma.
<On the other hand, MCT-3 and S-5 formulations were subjected to study focuses on their therapeutic activity against breast cancer cells.
Part II:
In-vitro/In-vivo evaluation of therapeutic activity of in-situ targeting of different Genistein-phospholipid complex formulations on hepatocellular carcinoma via oral route
Cellular uptake and cytotoxicity studies were carried out for S-5 and SA-3 on HepG2 cell line which is a cell line for hepatocellular carcinoma.
Anti-tumor effect of these formulation against liver cancer induced in mice was also evaluated.
Results show a potential cytotoxic effect for free Gen aglycone on HepG2 cell viability after application of Gen solution.
However, S-5 and SA-3 show good cytotoxic effects on HepG2 cell line for much long period than Gen solution owing to complex nature with SPC. Also anti-tumor study reveals the inapplicability for using S-5 and SA-3 in treatment of late stage of liver cancer disease.
However, S-5 and SA-3 possess good chemoprevention effect against HCC in early stages of liver cancer disease over Gen suspension.190
<Part III:
< Therapeutic efficacy of Genistein-phospholipid complex formulations on Breast Cancer treatment applying different routes of administration
Novel targeted formulations based on S-5 were prepared using HA and MPEG2000-DSPE (pegylated phospholipid).
HA was utilized as a targeting ligand for CD44 receptor found at the surface of breast cancer cells.
Formulations were administered via subcutaneous route. Pharmacokinetics and tissue distribution of subcutaneously administrated targeted formulations were carried out. Results reveal accumulation of G-PHA (Gen pegylated hyaluophytosome) compared to G-HA (Gen hyaluophytosomes). Evaluation of anti-tumor activity of targeted formulations against induced breast cancer in mice was carried out and results reveal a promising effect of G-PHA against breast cancer tumor after subcutaneous administration.
<In addition, change in route of administration of Gen phytosomes was evaluated against breast cancer cells.
This study was based on MCT-3 formulation owing to its effect in accumulating Gen in estrogenic tissues (genital organs) after oral administration. It is used in comparison with subcutaneous route of administration.
<Results reveal that oral administration of MCT-3 shows better anti-tumor effect against breast cancer cell compared to subcutaneous administration.