Effect of polymer architecture on the properties and in vitro cytotoxicity of drug formulation: A case study with mono- and di-gradient amphiphilic poly(2-Oxazoline)s.

Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.