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Researcher: Shashank Tummala
Guide(s): Gowthamarajan, K
Keywords: nanoparticles, survivin, Bcl-2, OP-SLN3 and OHNPs, colorectal tumors, immuno-nanoparticles
University: JSS University
Completed Date: 16/12/2015
Abstract: quotThe aim of this study is to prepare nanoparticles encapsulating oxaliplatin and later conjuagting them to TRAIL antibody covalently for improved site specificity along with apoptotic acitvity for colorectal tumors. newlineOxaliplatin was encapsualted into solid lipid nanoparticles and polymeric nanoparticles by microemulsion and solvent emulsification evaporation method respectively. The compatibility results demonstrated the compatibility of the excipients with the drug ensuring stability. Box-behnken design was used for the optimization of the nanoparticles. The nanoparticles optimized (OP-SLN3 and OHNPs) had shownappreciable particle size, drug loading and entrapment efficiency. In vitro drug release had shown biphasic pattern of drug release with initial burst release followedby sustained release later on. SEM and TEM studies confirmed the surface morphology of the nanoparticles. The immuno-nanoparticles were characterized for the confirmation of attachment of antibody by phycoerythrin nanoparticles visually and more homgenous distribution and intensity shift changes revealed by flow cytometry studies. In vitro cytotoxicity studies had shown enhanced apoptotic activity with IC50 values of 0.63 and#956;M for OIHNPs and 0.65 and#956;M for TR-OPSLN compared to the 3.5 and#956;M of oxalipaltin. Cellular uptake and internalization studies demonstrated the ability and specificity of the nanoparticles by their accumualtion in HT-29 cells rather than in MCF-7 cells and the co-culture studies further supported the cause. Flow cytometry studies revealed transitional S-phase delay at 72 h with G2/M cell cycle arrest. The immuno-nanoparticles were found to inhibit anti-apoptotic proteins (survivin, Bcl-2) and activate the apoptotic proteins confirmed by western blot analysis. newlineThe current drug therapy can lay a more improved foundation as an alternative to the present chemotherapy treatment by overcoming the limitations by delivering the drug to the target site specific to the protein. newlinequot newline
Pagination: I-XII, 1-1143p
Appears in Departments:College of Pharmacy

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01_title page.pdfAttached File99.54 kBAdobe PDFView/Open
02_certificates.pdf3.19 MBAdobe PDFView/Open
03_acknowledgement.pdf58.39 kBAdobe PDFView/Open
04_contents.pdf149.92 kBAdobe PDFView/Open
05_tablesfigures.pdf206.5 kBAdobe PDFView/Open
06_chapter 1.pdf1.26 MBAdobe PDFView/Open
07_chapter 2.pdf162.35 kBAdobe PDFView/Open
08_chapter 3.pdf608.41 kBAdobe PDFView/Open
09_chapter 4.pdf20.76 MBAdobe PDFView/Open
10_chapter 5.pdf166.47 kBAdobe PDFView/Open
11_chapter 6.pdf211.35 kBAdobe PDFView/Open
12_chapter 7.pdf61.69 kBAdobe PDFView/Open

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