*2.3. Batch Nanoprecipitation*

Polymer solutions with 5 mg mL−<sup>1</sup> or 2.5 mg mL−<sup>1</sup> were prepared in THF via batch nanoprecipitation. For the drug-loaded particles, 10 mg mL−<sup>1</sup> of BRP-187 dissolved in DMSO were mixed with the polymer solution prior to formulation, which corresponded to 3% (*w/w*) of the drug to polymer mass. The drug stock solution was sonicated in an ultrasound water bath for 15 min at room temperature to ensure good dissolution. Particle formulation was carried out by injecting the polymer/drug solution into an aqueous phase containing 0.3% (*w/v*) PVA using a syringe pump (Aladdin AL1000-220, World Precision Instruments, Berlin, Germany) with a flow rate of 2 mL min−<sup>1</sup> while stirring at 800 rpm. The solvent/non-solvent ratio was set to 1:8. The resulting particle suspensions were stirred for 24 h at room temperature for solvent evaporation and then centrifuged at 12.851 *x g* for 60 min at 20 ◦C using a Rotina 380 R centrifuge (Hettich Lab Technology, Tuttlingen, Germany). The supernatant was removed, and the NPs were redispersed in 2.5 mL pure water, vortexed and sonicated in an ultrasonic water bath for 30 min. The NPs were stored overnight at 4 ◦C and lyophilized in aliquots of 200 µL. After lyophilization, the mass of the NPs was determined using a precise analytical balance (MYA 11.4Y, Radwag Waagen, Hilden, Germany). The yield was calculated as follows: (mass of NPs recovered − mass of found PVA)/(mass of polymer + mass of drug) in the formulation × 100. To check reproducibility, five individual batches of the drug-loaded PCL particles were prepared and analyzed individually. The data provided represent the average values and the standard deviation of these five batches.
