1 research outputs found
Different Insight into Amphiphilic PEG-PLA Copolymers: Influence of Macromolecular Architecture on the Micelle Formation and Cellular Uptake
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)<sub>n</sub> (<i>n</i> = 1, 2 or 4; mPEG = polyÂ(ethylene glycol)
monomethylether 2K or 5K Da; PLA = atactic or isotactic polyÂ(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 mPEG<sub>2K</sub>-(PD,LLA)<sub>2</sub> 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)<sub><i>n</i></sub> 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 mPEG<sub>2K</sub>-(PD,LLA)<sub>2</sub> 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 mPEG<sub>2K</sub>-(PD,LLA)<sub>2</sub> was shown to be localized
inside the tumor cells. Indeed, the mPEG<sub>2K</sub>-(PD,LLA)<sub>2</sub> paclitaxel-loaded micelles mediate a potent antitumor cytotoxicity
effect