Microfluidic preparation and optimization of sorafenib-loaded poly (ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications

The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation effi-ciency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technolo-gies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(e-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation pro-cess and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribu-tion (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to