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  • Title: Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn H40, poly(L-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery.
    Author: Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S.
    Journal: Biomaterials; 2009 Jun; 30(16):3009-19. PubMed ID: 19250665.
    Abstract:
    Folate-conjugated amphiphilic hyperbranched block copolymer (H40-PLA-b-MPEG/PEG-FA) with a dendritic Boltorn H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell and a hydrophilic methoxy poly(ethylene glycol) (MPEG) and folate-conjugated poly(ethylene glycol) (PEG-FA) outer shell was synthesized as a carrier for tumor-targeted drug delivery. The block copolymer was characterized using (1)H NMR and gel permeation chromatography (GPC) analysis. Due to its core-shell structure, this block polymer forms unimolecular micelles in aqueous solutions. The micellar properties of H40-PLA-b-MPEG/PEG-FA block copolymer were extensively studied by dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). An anticancer drug, doxorubicin in the free base form (DOX) was encapsulated into H40-PLA-b-MPEG/PEG-FA micelles. The DOX-loaded micelles provided an initial burst release (up to 4h) followed by a sustained release of the entrapped DOX over a period of about 40 h. Cellular uptake of the DOX-loaded H40-PLA-b-MPEG/PEG-FA micelles was found to be higher than that of the DOX-loaded H40-PLA-b-MPEG micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. In vitro degradation studies revealed that the H40-PLA-b-MPEG/PEG-FA block copolymer hydrolytically degraded into polymer fragments within six weeks. These results indicated that the micelles prepared from the H40-PLA-b-MPEG/PEG-FA block copolymer have great potential as tumor-targeted drug delivery nanocarriers.
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