Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/175188
Title: DEVELOPMENT SAFETY AND EFFICACY EVALUATION OF SMART NANO CARRIERS FOR THE TREATMENT OF BREAST CARCINOMAS
Researcher: Venkata Siddhartha, T
Guide(s): Gowthamarajan, K
Keywords: Diallyl disulfide, Folic acid, Solid lipid nanoparticles, Breast cancer, Active targeting, folate-receptor mediated endocytosis.
University: JSS University
Completed Date: 30/11/2016
Abstract: Among the nanoparticles, various lipid nanoparticles namely, liposomes, solid lipid nanoparticles, nanostructured lipid carriers and lipid polymer hybrid nanoparticles have been developed over the years for the breast cancer therapy and evidences are documented.Utilizing the principles of quality by design approach, optimization of solid lipid nanoparticles (SLNs) formulation of Diallyl disulfide (DADS) through systematic statistical study was carried out. And further conjugation of Folic acid was carried out by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) for the active targeting of breast cancers. In vitro cytotoxicity studies, reactive oxygen species estimation study were performed. Internalization of FA-DADS-SLNs was evaluated by triple fluorescence staining method. Apoptosis determination was carried out by Annexin V-Propidium iodide assay and western blot analysis.FA-DADS-SLN exhibited the particle size 167± 1.72 nm, zeta potential 3.6 mv, entrapment efficiency was 69.76 ± 0.11%, and drug loading 29.75± 0.44%. Significant elevated cytotoxicity was observed with FA-DADS-SLNs in comparison to free DADS or DADS-SLNs. High intracellular uptake and higher apoptosis of DADS was observed by the delivery through FA-DADS-SLNs compared to DADS-SLN and free-DADS. Western blot analysis confirmed the intrinsic or mitochondrial mediated signalling pathway is the underlying mechanism for the apoptosis of FA-DADS-SLNs.In this study SLNs were employed for delivery of the DADS and to protect this short-lived bioactive substance. Folic acid conjugation made the lipid nanoparticles to target breast cancer cell lines. FA-DADS-SLNs which exhibited superior activity over DADS-SLNs which might be due to folate-receptor mediated endocytosis. FA-DADS-SLNs might be a suitable drug delivery system for targeting breast cancer and other folate receptor overexpressing cancers by achieving sustained release inside the tumor cells and enhancing the cytotoxicity of the DADS.
Pagination: I-XII, 1-71p
URI: http://hdl.handle.net/10603/175188
Appears in Departments:College of Pharmacy

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11.references.pdf194.86 kBAdobe PDFView/Open
1.title.pdf90.43 kBAdobe PDFView/Open
2.certificate.pdf127.18 kBAdobe PDFView/Open
3.acknowledgement.pdf142.36 kBAdobe PDFView/Open
4.contents.pdf21.99 kBAdobe PDFView/Open
5.list of tables.pdf144.37 kBAdobe PDFView/Open
6.preface.pdf31.54 kBAdobe PDFView/Open
7.chapter 1.pdf253.29 kBAdobe PDFView/Open
8.chapter 2.pdf155.3 kBAdobe PDFView/Open
9.chapter 3.pdf1.61 MBAdobe PDFView/Open
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