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Title: Targetting Drug resistant cancer stem like cells using nanoparticles A novel strategy for anticancer treatment
Researcher: Shaikh Muhammad
Guide(s): Nivsarkar Manish
Keywords: cancer
University: Nirma University
Completed Date: 12/06/2017
Abstract: Cancer has remained an enigma till date whose solution has evaded the inquisitive newlinescientific minds for long. In 2012 alone, cancer caused 8.2 million deaths globally and 14 newlinemillion new cases were reported. Current cancer therapies face several problems such as multi newlinedrug resistance, distant metastasis and the recurrence of the tumor post treatment. These newlineimpediments have been largely attributed to the presence of cancer stem cells (CSCs). Hence, newlinetargeting them could be a solution to the problems faced by current treatments. Biodegradable newlinepolymeric nanoparticles have greatly enhanced the targeted therapy scenario. Active and passive newlinetargeting, which they offer, has increased the therapies to reach the tumor site more efficiently. newlineSeveral reports indicate GLUT1 receptor to be overexpressed in cancer stem cells. newlineGlucosamine (GLN) is a strong ligand for the same. In our study we have developed two newlineformulations viz., Glucosamine coated doxorubicin loaded PLGA nanoparticles (GLN-DOXPLGA- newlineNPs) and Glucosamine coated paclitaxel loaded PLGA nanoparticles (GLN-PTXPLGA- newlineNPs) targeting the overexpressed GLUT1 receptors on drug resistant cancer stem-like newlinecells (DCSLCs). GLN-DOX-PLGA-NPs and GLN-PTX-PLGA-NPs were prepared using single newlineemulsion method and nanoprecipitation respectively. The formulation optimization was done newlineusing Box-Benken Design. The NPs were coated with GLN using carbodiimide chemistry. The newlineNPs were characterized for size, PDI and zeta potential using DLS. They were also newlinecharacterized using techniques like FTIR, DSC and TEM. Lastly, the NPs were checked for newlinecolloidal stability in ex-vivo conditions. newlineDrug resistant cancer stem-like cells (DCSLCs) were enriched from A549 and HepG2 newlinecells by gradually increasing the dose of DOX. DCSLCs were characterized using assays such newlineas sphere formation assay, soft agar colony formation assay, PCR, FACS analysis and tumor newlinexenograft formation. The DCSLCs were used to analyze the activity of the formulations. Cell newlineviability was performed using MTT and cellular uptake study wa
Appears in Departments:Institute of Pharmacy

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02_certificate.pdf267.28 kBAdobe PDFView/Open
03_abstract.pdf95.73 kBAdobe PDFView/Open
04_declaration.pdf313.73 kBAdobe PDFView/Open
05_acknowledgement.pdf34.71 kBAdobe PDFView/Open
06_contents.pdf75.44 kBAdobe PDFView/Open
07_list_of_tables.pdf109.95 kBAdobe PDFView/Open
08_list_of_figures.pdf407.23 kBAdobe PDFView/Open
09_abbreviations.pdf145.99 kBAdobe PDFView/Open
10_chapter1.pdf1.91 MBAdobe PDFView/Open
11_chapter2.pdf647.29 kBAdobe PDFView/Open
12_chapter3.pdf1.05 MBAdobe PDFView/Open
13_chapter4.pdf342.02 MBAdobe PDFView/Open
14_summary.pdf599.97 kBAdobe PDFView/Open
15_bibliography.pdf791.15 kBAdobe PDFView/Open
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