Tuesday, July 27, 2021

PLGA-PEG-Maleimide from PolySciTech used in the development of gefitinib loaded/p28 targeted nanoparticles for lung cancer treatment


Delivery of medicinal molecules to cancer cells is difficult based on the ability of the medicine to specifically target towards the tumor site as well as to cross into the cancer cell. This can be improved by attaching targeting ligands to the nanoparticles to improve their uptake. Recently, researchers at University of Lisbon, University of Porto, and CESPU-Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles for delivery of gefitinib to lung cancer. This research holds promise to improve treatment options for this fatal disease. Read more: Garizo, Ana Rita, Flávia Castro, Cláudia Martins, Andreia Almeida, Tiago P. Dias, Fábio Fernardes, Cristina C. Barrias, Nuno Bernardes, Arsénio M. Fialho, and Bruno Sarmento. "p28-functionalized PLGA nanoparticles loaded with gefitinib reduce tumor burden and metastases formation on lung cancer." Journal of Controlled Release (2021). https://www.sciencedirect.com/science/article/pii/S0168365921003783

“Abstract: Lung cancer is still the main cause of cancer-related deaths worldwide. Its treatment generally includes surgical resection, immunotherapy, radiotherapy, and chemo-targeted therapies such as the application of tyrosine kinase inhibitors. Gefitinib (GEF) is one of them, but its poor solubility in gastric fluids weakens its bioavailability and therapeutic activity. In addition, like all other chemotherapy treatments, GEF administration can cause damage to healthy tissues. Therefore, the development of novel GEF delivery systems to increase its bioavailability and distribution in tumor site is highly demanded. Herein, an innovative strategy for GEF delivery, by functionalizing PLGA nanoparticles with p28 (p28-NPs), a cell-penetrating peptide derived from the bacterial protein azurin, was developed. Our data indicated that p28 potentiates the selective interaction of these nanosystems with A549 lung cancer cells (active targeting). Further p28-NPs delivering GEF (p28-NPs-GEF) were able to selectively reduce the metabolic activity of A549 cells, while no impact was observed in non-tumor cells (16HBE14o-). In vivo studies using A549 subcutaneous xenograft showed that p28-NPs-GEF reduced A549 primary tumor burden and lung metastases formation. Overall, the design of a p28-functionalized delivery nanosystem to effectively penetrate the membranes of cancer cells while deliver GEF could provide a new strategy to improve lung cancer therapy. Keywords Azurin Cell penetrating peptide EGFR inhibitor Nanosized drug delivery system Active targeting Cancer therapy”

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