One-Pot Synthesis of Redox-Labile Polymer Capsules via Emulsion Droplet-Mediated Precipitation Polymerization

Abstract

Monodisperse poly(vinylcaprolactam) (PVCL)-based capsules are prepared by precipitation polymerization of vinylcaprolactam (VCL) onto dimethyldiethoxysilane (DMDES) emulsion droplets and removal of the DMDES templates by ethanol. Polymer chains in the shells can be cross-linked during the polymerization by disulfide-containing cross-linker N,N′-bis(acryloyl) cystamine, which endows the capsules with an excellent redox-labile property. Versatility of this technique to prepare capsules with diverse components is demonstrated by the copolymerization of methacrylic acid (MAA) and VCL in the shell to prepare poly(vinylcaprolactam-co-methacrylic acid) (P(VCL-co-MAA)) capsules. The disulfide-bonded capsules can degrade efficiently into low molecular weight species (ca. 1200 Da) when the capsules are incubated with 10 mM glutathione (GSH) as the reducing agent. Delivery of the anticancer drug (doxorubicin, DOX) was also investigated in the P(VCL-co-MAA) capsules. The cumulative in vitro release of DOX-loaded capsules allows a relatively low DOX release at pH 7.4. However, a burst release (ca. 90% in 6 h) of DOX was observed in the presence of 10 mM GSH. Cell viability assays show that the P(VCL-co-MAA) capsules have negligible cytotoxicity to HeLa cancer cells. In comparison, DOX-loaded P(VCL-co-MAA) capsules cause significant cell death following internalization. The reported capsules represent a novel and versatile class of stimuli-responsive carriers for controlled drug delivery.