signature=5daed8002ae3422211fb25bdea3c770f,(770b) Reductively Degradeable Polymeric Assemblies Const...

摘要：

Filamentous worm-like micelles constructed from amphiphilic diblcock copolymers are attractive nano-scale structures that have shown potential for application in drug delivery. The utility of these structures stems from their favorable physical attributes that resemble natural viruses. As a result, the worm-like micelles have shown significantly longer in-vivo circulation times compared to spherical assemblies such as micelles and vesicles. The functionality of these structures can be further enhanced if their degradation rates can be controlled in response to changes in physiologically relevant stimuli such as pH or temperature. Alternatively, we envisioned that the use of reduction potential as a trigger for worm-like micelle degradation would be an attractive strategy, particularly for the intra-cellular delivery of drugs as one can take advantage of the differences in reduction potential between the inside and outside of the cells. With that objective herein, we present the design, synthesis and characterization of a diblock copolymer, polyethyleneoxide-S-S-polycaprolactone (PEO-S-S-PCL), which self-assembles to form worm-like micelles and specifically undergoes degradation within a reducing environment. The stability of the PEO-S-S-PCL worm micelles investigated at different concentrations of reducing agents show that at millimolar range significant degradation is observed. Time lapse fluorescence microscopy studies show that the instantaneous rupture of the supra-molecular worm micelles occurs as a result of the molecular level reduction of the disulfide bond. Further, using a similar synthetic approach and by changing the block sizes a vesicular morphology can be obtained. Encapsulation and release of hydrophilic molecules from vesicles and hydrophobic molecules from worm micelles are currently being investigated.

展开