Pancreatic carcinoma (PC) is a severe malevolent form of cancer with a survival rate no more than 6% with a meager diagnosis. It ranks fourth among all cancer-related deaths in America and eighth worldwide. Until the advanced stages of pancreatic carcinoma it does not show any symptoms. FDA officially accepted gemcitabine (GEM) as a first-line treatment for patients when surgery is not a choice of treatment and for metastatic (stage IV) stage of the PC. Human Serum Albumin (HSA) is also approved as a drug carrier by the FDA. Next to GEM, Paclitaxel is a drug which has considerable anti-cancer activity. Nanoparticle Albumin Technology (Nab) was developed by Abraxis Biosciences to delivery paclitaxel (PTX) most efficiently at targeted site. GEM has a high hydrophilic character with poor plasma half-life which degraded to inactive products. To overcome it higher doses are administered to reach therapeutic concentrations which increase the risk of adverse effects. PTX is hydrophobic in nature and is not soluble in plasma; to overcome it we designed albumin bound nanoparticles. The main aim of the project is to develop novel albumin bound nanoparticles that encapsulates gemcitabine and paclitaxel to achieve the targeted drug delivery of PTX and to increase therapeutic concentration of gemcitabine in tumors. Albumin bound nanoparticles target tumor cells by two mechanisms - passive and active process. In passive process targeting action is achieved by EPR (enhanced permeability and retention). The active targeting process of albumin is facilitated by glycoprotein 60-mediated endothelial cell transcytosis. By binding nanoparticles to SPARC (secreted protein, acidic and rich in cysteine), GEM and PTX can accumulate in the tumor to achieve the desired therapeutic concentration and anti-cancer effects. The main objectives of this thesis are: 1. Preparation and characterization of GEM-PTX albumin bound nanoparticles. 2. Finding drug-loading percentage and encapsulation efficiency by using HPLC (high performance liquid chromatography) analysis. 3. Evaluating in vitro cytotoxicity of GEM-PTX albumin bound nanoparticles against Bxpc- 3 cell line.
Language
eng
File Type
pdf
File Size
643795 bytes
Date Available
January 9, 2018
LC Number
T378.24 A55p
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