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文獻名： Development of Targeted Polymeric Nanoparticles for Acute Myeloid Leukaemia

作者： Huanbutta, Kampanart; Teixeira, Maribel; Gonçalves, Virgínia; Tiritan, Elizabeth; Pinto, Madalena M. M.

摘要：Acute myeloid leukaemia (AML) is a severe disease due to the fast and excessive production of abnormal and immature myeloid blasts that causes an increased risk of anemia, bleeding and infections. The use of drug delivery systems is an efficient approach to overcome multidrug resistance in AML cells and can be targeted to these cells by the incorporation of homing molecules in their surface (e.g., attachment of folate (FOL) molecules that binds to folate receptors selectively expressed in leukaemia cells of approximay 70% of AML patients). Decitabine (DAC) is a DNA methyltransferase inhibitor used for the treatment of AML, but presents poor chemical stability (requiring complex dosage regimen) and produces several side effects. The aim of the present work was to develop and characterize new formulations of DAC-loaded folate-receptor targeted poly-lactide-co-glycolide-polyethylene glycol-nanoparticles (PLGA-PEG-FOL NPs) for the specific delivery to AML cells. Two different strategies for nanoparticle preparation were adopted, including the FOL attachment to previously prepared PLGA-PEG NPs and the synthesis of PLGA-PEG-FOL copolymer and further preparation of nanoparticles by double emulsion solvent diffusion technique. The results from 1H NMR and FTIR analysis show that PLGA-PEG-FOL was successfully synthesized. Nanoparticles had a mean diameter <284 nm, a spherical morphology, a narrow size distribution (polidispersity index <0.25), negative surface charge (–41.7 to –17.8 mV) and incorporation efficiency values ranging from 5.64 to 15.51%. Results suggest that the novel PLGA-PEG-FOL NPs could be a promising delivery system for targeting DAC to AML cells.

關鍵詞：ACUTE MYELOID LEUKAEMIA; DECITABINE; FOLATE RECEPTORS; NANOPARTICLES