title: Different insight into amphiphilic PEG-PLA copolymers: influence of macromolecular architecture on the micelle formation and cellular uptake.
abstract: One constrain in the use of micellar carriers as drug delivery systems (DDSs) is their low stability in aqueous solution. In this study "tree-shaped" copolymers of general formula mPEG-(PLA)n (n = 1, 2 or 4; mPEG = poly(ethylene glycol) monomethylether 2K or 5K Da; PLA = atactic or isotactic poly(lactide)) were synthesized to evaluate the architecture and chemical composition effect on the micelles formation and stability. Copolymers with mPEG/PLA ratio of about 1:1 wt/wt were obtained using a "core-first" synthetic route. Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscopy (FESEM), and Zeta Potential measurements showed that mPEG2K-(PD,LLA)2 copolymer, characterized by mPEG chain of 2000 Da and two blocks of atactic PLA, was able to form monodisperse and stable micelles. To analyze the interaction among micelles and tumor cells, FITC conjugated mPEG-(PLA)n were synthesized. The derived micelles were tested on two, histological different, tumor cell lines: HEK293t and HeLa cells. Fluorescence Activated Cells Sorter (FACS) analysis showed that the FITC conjugated mPEG2K-(PD,LLA)2 copolymer stain tumor cells with high efficiency. Our data demonstrate that both PEG size and PLA structure control the biological interaction between the micelles and biological systems. Moreover, using confocal microscopy analysis, the staining of tumor cells obtained after incubation with mPEG2K-(PD,LLA)2 was shown to be localized inside the tumor cells. Indeed, the mPEG2K-(PD,LLA)2 paclitaxel-loaded micelles mediate a potent antitumor cytotoxicity effect.
authors: Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Graecia" di Catanzaro , viale Europa, Catanzaro 88100, Italy.
authors: Cinzia
authors: C
authors: Garofalo
authors: Giovanna
authors: G
authors: Capuano
authors: Rosa
authors: R
authors: Sottile
authors: Rossana
authors: R
authors: Tallerico
authors: Renata
authors: R
authors: Adami
authors: Ernesto
authors: E
authors: Reverchon
authors: Ennio
authors: E
authors: Carbone
authors: Lorella
authors: L
authors: Izzo
authors: Daniela
authors: D
authors: Pappalardo
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry* / Q000378:metabolism
chemical_list: D046911:Macromolecular Substances; D008823:Micelles; D013501:Surface-Active Agents; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols