Modular Control of PEG-Poly(2-Oxazoline) Co-Assembly Enables Tunable Aggregate Properties for Intraocular Pressure Management.

Poly(2-oxazoline) (POx) polymers are hydrophilic and biocompatible materials with tunable physicochemical properties for biomedical use. Postoperative hypotony, which currently lacks approved pharmacological or device-based treatment, requires minimally invasive and controllable methods for temporary intraocular pressure restoration. Herein, we present a modular strategy to control POx aggregation via thermally triggered co-assembly with thermoswitchable poly(2-n-propyl-2-oxazoline) (PnPrOx) and hydrophilic PEG-modified PnPrOx (PnPrOx-PEG). These mixtures remain dissolved at low temperatures but aggregate at physiological temperatures because of the thermo-switchable behavior of the PnPrOx segments, with PEG content modulating particle size, dispersibility, and fusion. Based on in vivo compositional screening in rabbits, we highlight a 98:2 (w/w) PnPrOx:PnPrOx-PEG formulation (POx2P) that induces transient intraocular pressure elevation without persistent turbidity or deposition. In a trabeculectomy-induced hypotony model, POx2P restored intraocular pressure without adverse effects. Microscopy and in vivo imaging suggest that this formulation forms flow-responsive aggregates that transiently occlude aqueous outflow pathways. We established a compositionally tunable and injectable POx platform for in situ aggregation and pressure modulation, offering a clinically relevant approach for localised intraocular therapy.