Novel self-assembled nanogels of PEG-grafted poly HPMA with bis(α-cyclodextrin) containing disulfide linkage: synthesis, bio-disintegration, and in vivo biocompatibility

Synthesis of a self-assembled supramolecular network was achieved through host-guest chemistry between the inter-molecularly crosslinked α-cyclodextrin with cystamine linker (bisCD) and the random copolymer of poly HPMA and PEG acrylate (P(HPMA-MPEGA) synthesized by RAFT polymerization. Compared to α-CD, bisCD caused strong PEG chain aggregation, resulting in nanogel production at lower concentrations. DSC, TGA, XRD, ¹H-NMR and FT-IR confirmed the interaction between PEG chains and bisCD that resulted in the formation of the pseudo-rotaxane complex structure. Depending on the bisCD concentration, particle size, gelation time, and mechanical strength could be tuned. As shown by SEM, nanogels of about 158 ± 39 nm were generated under optimized conditions. In addition, the rate of bisCD nanogel disintegration was accelerated by more than one order of magnitude in phosphate buffer (pH 7.4) after the addition of urea. Hemolysis and histopathology assays also confirmed the in vivo biocompatibility of the bisCD nanogels. Therefore, the bisCD nanogels could be regarded as a new soft nanomaterial for biomedical applications.