Redox-Responsive Disulfide Cross-Linked PLA–PEG Nanoparticles

• Published in: Macromolecules 2017-09, Vol.50 (18), p.7052-7061
• Main Authors: Fuoco, Tiziana, Pappalardo, Daniela, Finne-Wistrand, Anna
• Format: Article
• Language: English
• ISSN: 0024-9297; 1520-5835; 1520-5835
• DOI: 10.1021/acs.macromol.7b01318

We have developed a strategy for the preparation of redox-responsive PEG–PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly­(lactide)­s were prepared by ring-opening copolymerization of l-lactide and 3-methyl-6-(tritylthio­methyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide 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 a hydrophobic core and a hydrophilic shell, with sizes in the range 167–300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.