Combined Core Stability and Degradability of Nanomedicine via Amorphous PDLLA-Dextran Bottlebrush Copolymer for Alzheimer’s Disease Combination Treatment

Nanomedicine faces the challenges of infinite dilution, shear force, biological protein, or electrolyte competition. However, core cross-linking leads to biodegradability deficiency and brings inevitable side effects of nanomedicine on normal tissues. In order to overcome this bottleneck problem, we turn to amorphous poly(d,l)lactic acid (PDLLA)-dextran bottlebrush to emphasize the core stability of nanoparticles, and the amorphous structure offers an additional advantage of fast degradation property over the crystalline PLLA polymer. The graft density and side chain length of amorphous PDLLA together played important influence roles in controlling the architecture of nanoparticles. This effort produces structure-abundant particles, including micelles, vesicles, and large compound vesicles after self-assembly. Here, the amorphous bottlebrush PDLLA was verified to play a beneficial role in the structure stability and degradability of nanomedicines. The codelivery of the hydrophilic antioxidant of citric acid (CA), vitamin C (VC), and gallic acid (GA) via the optimum nanomedicines could effectively repair the SH-SY5Y cell damage caused by H2O2. The CA/VC/GA combination treatment repaired the neuronal function efficiently, and the cognitive abilities of senescence-accelerated mouse prone 8 (SAMP8) recovered.