Direct Comparison of Analogous Amphiphilic Gradient and Block Polyoxazolines

Both gradient and block copolymers can be used as drug delivery systems, but their relative (dis)­advantages remain unknown. Thus, we directly compared analogous amphiphilic gradient and block polyoxazolines for their physicochemical properties and potential as building components of nanodrugs. For this purpose, we prepared a library of 18 polymers with varying ratios of monomeric units, using 2-methyl-2-oxazoline (MeOx) as a hydrophilic monomer and 2-phenyl-2-oxazoline (PhOx), 2-(4-butylphenyl)-2-oxazoline (BuPhOx), or 2-(4-butoxyphenyl)-2-oxazoline (BuOPhOx) as a hydrophobic monomer, and determined their homo/heteropolymerization kinetics. Our results showed that gradient copolymers had broader glass transition intervals and formed nanoparticles several times smaller and more compact than the corresponding block analogs. In particular, PMeOx70-grad-PhOx30 and PMeOx70-grad-BuPhOx30 exhibited a significantly higher drug loading capacity and entrapment efficiency than their corresponding block analogs. Notwithstanding these differences, all polymers were cyto- and hemocompatible in vitro. Therefore, analogous gradient and block copolymers may be alternatively used for specific biomedical applications.