Wednesday, August 15, 2018

PLGA-PEG-COOH from PolySciTech used in development of antigen-labelled nanoparticles for colorectal cancer therapy




Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The severe side effects of most chemotherapeutics used for treating this cancer limit their dosage. Use of a delivery system to improve uptake of the medicinal molecules to the cancer site can improve efficacy and reduce side-effects. Recently, researchers at Universidade do Porto, Universitario de Ciencias da Saude (Portugal), and Queen’s University Belfast (UK) used PLGA-PEG-COOH (PolyVivo AI076) from PolySciTech (www.polyscitech.com) to generate paclitaxel-loaded nanoparticles with –COOH groups along the exterior. They used carbodiimide/NHS conjugation methodologies to attach a carcinoembryonic antibody to the exterior of the particle for ligand-attachment to cancer cells. This research holds promise for improved therapies for colorectal cancer. Read more: Pereira, Ines, Flavia Sousa, Patrick Kennedy, Bruno Sarmento “Carcinoembryonic antigen-targeted nanoparticles potentiate the delivery of anticancer drugs to colorectal cancer cells” International Journal of Pharmaceutics Volume 549, Issues 1–2, 5 October 2018, Pages 397-403 https://www.sciencedirect.com/science/article/pii/S0378517318305787

“Abstract: Bioengineered functionalized nanoparticles have extensively been proposed in recent years to efficiently deliver anti-cancer drugs to the tumour site, by targeting the cancer cells and improving the therapeutic efficiency of active molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethylene glycol (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with paclitaxel, following surface-functionalized with a monoclonal antibody targeting the carcinoembryonic antigen (CEA) of intestinal epithelial cells. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed successful production of nanoparticles around 200 nm, and close to charge neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles were further constructed, demonstrating to be non-cytotoxic against intestinal cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting antibody were successfully developed as nanocarriers for paclitaxel and interacted with CEA expressing cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics. Keywords: Drug delivery Carcinoembryonic antigen Targeted nanoparticles Colorectal cancer”

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