Synthesis and Investigation of Chiral Poly(2,4-disubstituted-2-oxazoline)-Based Triblock Copolymers, Their Self-Assembly, and Formulation with Chiral and Achiral Drugs

Abstract

Considering the largely chiral nature of biological systems, there is interest in chiral drug delivery systems. Here, we investigate for the first time polymer micelles based on poly(2-oxazoline) (POx) ABA-type triblock copolymers with chiral and racemic hydrophobic blocks for the formulation of chiral and achiral drugs. Specifically, poly(2-ethyl-4-ethyl-2-oxazoline) (pEtEtOx) and poly(2-propyl-4-methyl-2-oxazoline) (pPrMeOx) were used as hydrophobic block B and poly(2-methyl-2-oxazoline) (pMeOx) as hydrophilic block A. Using these triblock copolymers, nanoformulations of curcumin (CUR), paclitaxel (PTX), and chiral (R and S) and racemic ibuprofen were prepared. For CUR and PTX, the maximum drug loading was significantly dependent on the structure of the hydrophobic repeat units, but not the chirality. In contrast, the maximum drug loading with chiral/racemic ibuprofen was affected neither by the polymer structure nor by chirality, but minor effects were observed with respect to the size and size distribution of the drug-loaded micelles.