Add time:07/23/2019         Source:sciencedirect.com

A series of amphiphilic 4- and 6-armed star triblock co-polymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (4/6AS-PCL-b-PDEAEMA-b-PPEGMA) were developed by a combination of ring opening polymerization and continuous activators regenerated by electron transfer atom transfer radical polymerization. The critical micelle concentration values of the star co-polymers in aqueous solution were extremely low (2.2–4.0 mg l–1), depending on the architecture of the co-polymers. The self-assembled blank and doxorubicin (DOX)-loaded three layer micelles were spherical in shape with an average size of 60–220 nm determined by scanning electron microscopy and dynamic light scattering. The in vitro release behavior of DOX from the three layer micelles exhibited pH-dependent properties. The DOX release rate was significantly accelerated by decreasing the pH from 7.4 to 5.0, due to swelling of the micelles at lower pH values caused by the protonation of tertiary amine groups in DEAEMA in the middle layer of the micelles. The in vitro cytotoxicity of DOX-loaded micelles to HepG2 cells suggested that the 4/6AS-PCL-b-PDEAEMA-b-PPEGMA micelles could provide equivalent or even enhanced anticancer activity and bioavailability of DOX and thus a lower dosage is sufficient for the same therapeutic efficacy. The results demonstrate that the pH-sensitive multilayer micelles could have great potential application in delivering hydrophobic anticancer drugs for improved cancer therapy.

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