Redox-Responsive Disulfide Cross-Linked PLA−PEG Nanoparticles

We have developed a strategy for the preparationof redox-responsive PEG−PLA-based nanoparticles containingdisulfide bonds that can be disassembled in the presence ofcellular concentrations of glutathione. Functionalized poly-(lactide)s were prepared by ring-opening copolymerization of Llactideand 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione,a monomer bearing a pendant trityl-thiol group, followed by thepostpolymerization modification of trityl-thiol into pyridyldisulfide groups. Polymeric networks composed of PLA andPEG blocks linked by disulfide bonds were prepared by adisulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH,in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having ahydrophobic core and a hydrophilic shell, with sizes in the range 167−300 nm that are suitable for drug delivery. The effects ofthe number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability ofthe nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione wereassessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence ofglutathione at cellular concentration.