Novel self-assembled pH-responsive biomimetic nanocarriers for drug delivery

Novel pH-responsive biodegradable biomimetic nanocarriers were prepared by the self-assembly of N-acetyl-L-histidine-phosphorylcholine-chitosan conjugate (NAcHis-PCCs), which was synthesized via Atherton-Todd reaction to couple biomembrane-like phosphorylcholine (PC) groups, and N,N'-carbonyldiimidazole (MI) coupling reaction to link pH-responsive N-acetyl-L-histidine (NAcHis) moieties to chitosan. In vitro biological assay revealed that NAcHis-PCCs nanoparticles had excellent biocompatibility to avoid adverse biological response mainly owing to their biomimetic PC shell, and DLS results confirmed their pH-responsive behavior in acidic aqueous solution (pH <= 6.0). Quercetin (QUE), an anti-inflammatory, antioxidant and potential anti-tumor hydrophobic drug, was effectively loaded in NAcHis-PCCs nanocarriers and showed a pH-triggered release behavior with the enhanced QUE release at acidic pH 5.5 compared to neutral pH 7.4. The results indicated that pH responsive biomimetic NAcHis-PCCs nanocarriers might have great potential for site-specific delivery to pathological acidic microenvironment avoiding unfavorable biological response. (C) 2016 Elsevier B.V. All rights reserved.