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Title: Trastuzumab-decorated nanoparticles of biodegradable polymers for targeted small molecule chemotherapy
Keywords: Cancer nanotechnology,Nanomedicine,Nanoparticles,Paclitaxel,Docetaxel,Herceptin
Issue Date: 13-Aug-2009
Citation: SUN BINGFENG (2009-08-13). Trastuzumab-decorated nanoparticles of biodegradable polymers for targeted small molecule chemotherapy. ScholarBank@NUS Repository.
Abstract: Targeted chemotherapy has been a challenge in Nanomedicine. This PhD work developed two novel drug delivery systems of Trastuzumab-decorated nanoparticles (NPs) of biodegradable polymers for targeted chemotherapy with Taxoids (Paclitaxel and Docetaxel) as model small molecule therapeutics. Trastuzumab (Herceptin®) is a FDA-approved humanized monoclonal antibody drug which is effective for the cancer of human epidermal growth factor receptor-2 (HER2) overexpression. It is also found synergistic with Taxoids. The first system is the paclitaxel-loaded poly(D,L-lactide-co-glycolide)/montmorillonite (PLGA/MMT) NPs with Trastuzumab physically adhered on the NP surface. The second system is the Docetaxel-loaded NPs of a blend of two novel copolymers. One is poly(lactide)-D-a-tocopheryl polyethylene glycol succinate (PLA-TPGS), which is of ideal hydrophobic-lipophilic balance for high drug encapsulation efficiency and high cellular adhesion, and another is carboxyl group-terminated TPGS (TPGS-COOH), which facilitates the antibody conjugation on the nanoparticle surface. The targeting effect can be quantitatively controlled by adjusting the copolymer blend ratio. The NPs were prepared by a modified solvent extraction/evaporation method and characterized by state-of-the art equipment for their physicochemical and pharmaceutical properties such as size and size distribution, surface morphology, surface chemistry, surface charge, drug encapsulation efficiency, in vitro drug release kinetics. Proof-of-concept in vitro experimental evaluation showed that the Trastuzumab-functionalized NPs have great advantages versus the corresponding nude NPs in cellular uptake and cytotoxicity for cancer cells of HER2 overexpression.
Appears in Collections:Ph.D Theses (Open)

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