Nanocarriers-encapsulating phytochemicals as potent therapeutics in cancer therapy

Radhakrishnan, R 2017, Nanocarriers-encapsulating phytochemicals as potent therapeutics in cancer therapy, Doctor of Philosophy (PhD), Science, RMIT University.

Document type: Thesis
Collection: Theses

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Title Nanocarriers-encapsulating phytochemicals as potent therapeutics in cancer therapy
Author(s) Radhakrishnan, R
Year 2017
Abstract Cancer is a disease concerning the abnormal, uncontrolled growth of cells that possess a potential to invade and injure other parts of the body. Chemotherapy involves administration of drugs targeted towards the mechanisms responsible for this rapid division and proliferation. However, most chemotherapy drugs are non-specific, also causing allied toxicity to normal cells undergoing cell division.

In this work, phytochemicals were used as anti-cancer drugs. These molecules are non-toxic and biocompatible. However, they also display striking anti-cancer potential, which was explored in this thesis. In this work, epigallocatechin gallate, piperine and mangiferin have been explored for their anti-cancer efficacy.

Although phytochemicals are effective agents in cancer chemotherapy, many of them suffer from disadvantages such as pH instability and limited bioavailability in the body. To address this problem, nanocarriers were designed to facilitate their increased bioavailability and stability inside the body. Two nanoparticle matrices were explored in this work; solid lipid nanoparticles and chitosan nanoparticles. Solid lipid nanoparticles were used as they are biocompatible, help improve drug stability and show controlled release. Chitosan nanoparticles are biodegradable, biocompatible and have shown excellent absorption properties for chemotherapeutic drugs.

Chemotherapy mainly deals with two targeting approaches; active and passive. While passive targeting relies on the characteristics of the tumour for effective therapy, active targeting involves attachment of ligands on the nanocarrier for more specific targeting. Both the targeting approaches have been explored in this work. In addition, two targeting ligands were used in this work; bombesin and mannose, which are specific for factors overexpressed in cancer.

In summary, this thesis involves the design and fabrication of nanocarriers in order to increase the anti-cancer efficacy of phytochemicals, utilising different targeting approaches, matrix components and targeting ligands. The anti-cancer efficacy was evaluated by in-vitro cytotoxicity studies and in-vivo animal studies. The results validate the increased anti-cancer efficacy provided by the encapsulation of the drugs within nanocarrier systems thus offering encouraging, novel possibilities in the field of cancer therapy.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Science
Subjects Nanomaterials
Cell Development, Proliferation and Death
Keyword(s) Nanoparticles
Drug delivery
Epigallocatechin gallate
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Created: Wed, 29 Nov 2017, 12:48:48 EST by Denise Paciocco
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