1 research outputs found
Organocatalytic Synthesis and Evaluation of Polycarbonate Pendant Polymer:β-Cyclodextrin-Based Nucleic Acid Delivery Vectors
A family
of mPEG-<i>b</i>-polycarbonate (mPEG-PC) diblock
pendant polymers were synthesized from trimethylene carbonate and
other cyclic carbonate monomers bearing hydrophobic guest ligands
via organocatalytic ring-opening polymerization using 1,4,5-triazabicyclo[4.4.0]Âdec-5-ene
catalyst or 1,8-diazabicyclo[5.4.0]Âundec-7-ene/thiourea cocatalyst.
Diblock copolymers composed of a methoxyÂpolyÂ(ethylene oxide)
(mPEG) block and a polycarbonate block containing either homopolymer
or mixed polycarbonates (PC) were prepared by homopolymerization or
copolymerization of the cyclic carbonate monomers in the presence
of mPEG2000 or mPEG5000 initiator to give materials having a tunable
pendant group density along the polycarbonate backbone. Polycarbonate
blocks targeting the 2.4–10 kDa range were prepared with good
molecular weight control and modest polydispersities (averaging ∼1.3).
Complexation of plasmid DNA with β-cyclodextrin–polyethylenimine2.5
kDa produced nanoparticle cores that were then coated with the mPEG–PC
diblock copolymers to produce transfection complexes in the 100–250
nm size range. Stable transfection complexes prepared at N/P ratios
>10 had slightly positive ζ potentials and showed comparable
or modestly better transfection efficiencies in HeLa cells than the
commercial transfection agent, Lipofectamine2000. Transfection efficiencies
were not dependent on polycarbonate block molecular weights. The mPEG-PC
constructs displayed similar efficacy for adamantyl and cholesteryl
pendants that strongly bind to β-cyclodextrin; however, slightly
better performance was observed for the weakly bound pendant, benzyl.
These findings suggest that pDNA release is largely mediated by hydrolysis
of the ester-bound pendant ligand within the endolysosomal compartment
of the cell, with desorption of the mPEG–PC layer also contributing
to plasmid release and activation in the case of weak binding pendant
groups. We infer from these results that mPEG-PC may be an effective
degradable transfection agent for <i>in vivo</i> applications