pH‐Responsive Nanoparticles for Controllable Curcumin Delivery: The Design of Polycation Core with Different Structures

Abstract

To achieve low leakage at pH 7.4, pH‐controlled drug release remains a major challenge of cancer nanomedicine. Here, pH‐responsive mPEG113‐b‐polycaprolactone (PCL)x‐b‐PAEMAy (PELAx) nanoparticles (NPs)‐pH7.4 with different poly(2‐azepane ethyl methacrylate) (PAEMA) lengths and PELA4 nanoparticles (NPs)‐pHx with different pH conditions of preparing NPs based on mPEG113‐b‐PCLx‐b‐PAEMAy are prepared to investigate influences of PAEMA lengths and pH condition of preparing NPs on properties of NPs. PELAx NPs‐pH7.4 and PELA4 NPs‐pHx both undergo differently sharp property changes of size, charge, pH‐responsive drug release, cellular uptake, and cytotoxicity, because of the protonation of PAEMA block (pKa ≈ 6.5–6.7). Among PELAx NPs‐pH7.4 and PELA4 NPs‐pHx, it can be found that the NPs prepared at pKa value of PAEMA exhibited exciting pH‐responsive drug release, improving cellular uptake ability and obvious high cytotoxicity toward HepG‐2 cells. This system not only holds great potential for drug delivery but also provides a new strategy to prepare pH‐responsive NPs.

pH-responsive polymeric nanoparticles with tunable sizes for targeted drug delivery

“…The hydrolysis of Schiff base linkages can only start from the NPs surface in weakly acid conditions and slowly penetrate the interior of the NPs, leading to the shrinkage of the core, while the shell becomes swollen and loose. [43][44][45][46] Among the three kinds of NPs in aqueous solutions at pH 4.0, the stability of the NPs changed in the following order: NPs-O 1:1 > NPs-H 1:1 > NPs-R 1:1 . Therefore, the larger the side chains are for the formation of NPs, the more difficult it is for H + to penetrate the interior of the NPs to disassemble hydrophobic cores.…”