Influence of supramolecular layer-crosslinked structure on stability of dual pH-Responsive polymer nanoparticles for doxorubicin delivery

Undesired physiological instability remains a major limitation for nanoparticle-based drug delivery. To overcome this issue, a dual pH-responsive supramolecular layer-crosslinked nanoparticles (PCB-b-PCD/PBM-b-PDPA NPs, PDM NPs), which consisted of pH-responsive hydrophobic poly(diisopropylethyl methacrylate) (pKa ≈6.3) as the core, hydrophilic poly((methacrylic acid betaine) methyl methacrylate) as the shell and pH-responsive supramolecular crosslinked layer based on β-cyclodextrin and benzimidazole (pKa <6.0), was prepared. Effects of this supramolecular layer-crosslinked structure on dilution and stored stability, protein adsorption, and pH-responsibility were investigated. PDM NPs exhibited lower critical aggregation concentrations, good unimodal distribution and better dilution stability in comparison with non-crosslinked PCB-PDPA NPs. Moreover this pH-responsive supramolecular layer-crosslinked structure did not only influence the anti-protein adsorption ability, but also reduced the disintegrated pH (from 6.3 to below 6.0) of PDM NPs, which leads to the DOX was released from PDM NPs at the mildly acid condition effectively and sustainably in vitro. Therefore, this pH-responsive layer-crosslinked NPs held promising potentials as a smart nanocarriers for drug delivery.