In-depth study of anticancer drug diffusion through a cross-linked ­pH-responsive polymeric vesicle membrane

Abstract

Post-encapsulation and release of the anticancer drug doxorubicin hydrochloride (DOX·HCl) through cell-like transmission functions of polymeric vesicles were studied using cross-linked pH-responsive polymeric vesicles. The vesicles were fabricated for the first time via the redox-initiated reversible addition-fragmentation chain transfer dispersion polymerization in ethanol-water mixture, using 2-(diisopropylamino)ethyl methacrylate and glycidyl methacrylate, and the vesicle membrane was modified post-cross-linking by using ethylenediamine. A phase diagram was constructed for reproducible fabrication of the polymeric vesicles, and well-shaped vesicles were formed when the target degree of polymerization of the hydrophobic polymer chains was equal to or higher than 50 with solid content in the range of 10–30 wt%. The cross-linked vesicle membrane served as a gate enabling “open” and “closed” states in response to pH stimulation. Up to 50% drug loading efficiency and 39% drug loading content could be achieved, and in vitro release of the DOX-loaded vesicles in aqueous buffer solutions showed a much faster DOX release rate at pH 5.0 than at pH 6.5. The polymeric vesicles were of very low cytotoxicity to A549 cells up to the concentration of 2 mg/mL, and the IC 50 of DOX-loaded vesicles were higher than that of the free DOX. The intracellular DOX release study indicated higher cellular uptake capability for DOX-loaded vesicles than that of free DOX.

In Situ Fabrication of Silver Nanoparticle‐Decorated Polymeric Vesicles for Antibacterial Applications

“…In this study, the in situ deposition of AgNPs on polymeric vesicles was conducted using cross‐linked polymeric vesicles as templates. Polymeric vesicles mPEG‐b‐P(DIPEMA‐co‐GlyMA) were produced through redox‐initiated RAFT dispersion polymerization, as previously reported [31] . The cross‐linking of the vesicle membrane was conducted using ethylenediamine (EDA) to react with the epoxy groups on the vesicles, to improve the stability.…”

“…Polymeric vesicles mPEG‐b‐P(DIPEMA‐co‐GlyMA) were produced through redox‐initiated RAFT dispersion polymerization, as previously reported. [31] The cross‐linking of the vesicle membrane was conducted using ethylenediamine (EDA) to react with the epoxy groups on the vesicles, to improve the stability. In addition, a certain number of amine groups were further introduced into the vesicles, as reported by Tan et al.…”

“…Polymeric vesicles mPEG-b-P(DIPEMA-co-GlyMA) were produced through redox-initiated RAFT dispersion polymerization, as previously reported. [31] The cross-linking of the vesicle membrane was conducted using ethylenediamine (EDA) to react with the epoxy groups on the vesicles, to improve the stability. In addition, a certain number of amine groups were further introduced into the vesicles, as reported by Tan et al [32] for poly(glycerol monomethacrylate) 46 -b-poly(2-hydroxypropyl methacrylate) 300 -bpoly(glycidyl methacrylate) 300 vesicles, where free amine groups were introduced through epoxydiamine chemistry.…”

“…By using cross‐linked polymeric vesicles as the template, AgNPs were fabricated in situ on vesicle membranes via the reduction of AgNO 3 using PVP through coordination bonds between the Ag + ions and nitrogen atoms on the vesicles. The vesicles were produced by redox‐initiated reversible addition‐fragmentation chain transfer (RAFT) dispersion polymerization with a 2‐(diisopropylamino)ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) in an ethanol–water mixture, and the vesicle membranes were cross‐linked through the post‐polymerization of epoxydiamine chemistry, as reported in our previous study [31] . The PDIPEMA blocks on the vesicles allowed the nitrogen atoms to coordinate with the Ag + ions, and cross‐linking of the vesicle membrane initially improved vesicle stability and introduced more amine groups, improving the attachment ability with Ag + ions [17,32,33] .…”

“…The vesicles were produced by redox‐initiated reversible addition‐fragmentation chain transfer (RAFT) dispersion polymerization with a 2‐(diisopropylamino)ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) in an ethanol–water mixture, and the vesicle membranes were cross‐linked through the post‐polymerization of epoxydiamine chemistry, as reported in our previous study. [31] The PDIPEMA blocks on the vesicles allowed the nitrogen atoms to coordinate with the Ag + ions, and cross‐linking of the vesicle membrane initially improved vesicle stability and introduced more amine groups, improving the attachment ability with Ag + ions. [ 17 , 32 , 33 ] Subsequently, XRD, UV‐vis, and TEM analyses were applied to investigate the formation of AgNP‐decorated vesicles, and their antibacterial properties were evaluated.…”