Abstract
Methoxy-poly(ethylene glycol)-poly(l-glutamic acid)-poly(l-phenylalanine) triblock polymers with different architecture were synthesized as drug carrier to obtain sustained and controlled release by tuning the composition. These triblock polymers were prepared by ring opening polymerization and poly(ethylene glycol) was used as an initiator. Polymerization was confirmed by 1H NMR, FT-IR and gel penetration chromatography. The polymers can self-assemble to form micelles in aqueous medium and their critical micelle concentrations values were examined. The micelles were spherical shape with size of 50–100 nm and especially can arranged in a regular manner. Sorafenib was selected as the model drug and the drug loading performance was dependent on the composition of the block copolymer. In vitro drug release indicated that the polymers can realize controlled and sustained drug release. Furthermore, in vitro cytotoxicity assay showed that the polymers were biocompatible and the drug-loaded micelles can increase toxicity towards tumor cells. Confocal fluorescence microscopy assays illustrated that the micelles can be uptaken quickly and release drug persistently to inhibit tumor cell growth.
Highlights
According to the USA Food Drug Administration, the approved number of new drugs has declined to 25% in 2000–2010 compared with that in 1990–2000 [1]
Though poly(L-glutamic acid) (PLGA)-PPA copolymers have characteristic properties, their stability in the blood circulation is inadequate for the tumor targeting drug delivery
Both the 1H nuclear magnetic resonance (NMR) and Fourier transform-infrared spectroscopy (FT-IR) spectra conclusively proved that the Methoxy-poly(ethylene glycol) (mPEG)-PLGA-PPA triblock copolymer was successfully synthesized
Summary
According to the USA Food Drug Administration, the approved number of new drugs has declined to 25% in 2000–2010 compared with that in 1990–2000 [1]. By appropriate modification of the molecule structure, a variety of polypeptide copolymers can be designed to possess varying degrees of hydrophobicity, structural attributes, and electrostatic properties [11] Both poly(L-glutamic acid) (PLGA) and poly(L-phenylalanine) (PPA) are typical blocks utilized to form polypeptides as drug carriers [12]. Though PLGA-PPA copolymers have characteristic properties, their stability in the blood circulation is inadequate for the tumor targeting drug delivery. PEG provides a compact steric protective corona layer to maintain the stability of micelles during biological circulation, and PLGA, as backbone chains, forms the shell of micelles. The hydrophobic PPA forms the core of micelles and was intended to allocate significant amounts of hydrophobic drugs and sustains the drug release These copolymers can self-assemble to micelles in aqueous solution. Cell cytotoxicity and tumor cell uptake behavior of micelles have been explored to evaluate the potential for in vivo drug delivery
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