Hierarchical paclitaxel encapsulation in microbead-embedded microparticles for sustained ovarian cancer therapy

Ovarian cancer (OC) is the most lethal gynecologic malignancy, often diagnosed at advanced stages due to clinically silent peritoneal carcinomatosis. Although intraperitoneal (IP) chemotherapy enhances drug exposure, its effectiveness is hindered by rapid clearance, toxicity, and uneven distribution. To address these challenges, we developed a novel drug delivery system integrating paclitaxel (PTX)-loaded poly(lactic-co-glycolic acid) microparticles (PLGA-MPs) within calcium-alginate microbeads (Alg-MBs). This system aims to provide sustained drug release while minimizing adverse effects. PTX-loaded PLGA-MPs were prepared via solvent evaporation and encapsulated in Alg-MBs using a coaxial air jet generator. In vitro studies showed an initial burst release over five days, followed by sustained release until day 21, confirming the role of Alg-MBs in modulating drug diffusion. Cytotoxicity tests in 2D SKOV-3 OC cultures revealed dose-dependent effects, with increased PTX concentrations reducing cell viability. A 3D bioprinted tumor model was used to better replicate in vivo conditions and evaluate long-term efficacy. Sustained PTX release resulted in progressive tumor cell death over 21 days, with delayed but potent cytotoxicity at higher doses. These findings support hierarchical PTX microencapsulation for prolonged IP chemotherapy, while the 3D bioprinted model provided a more physiologically relevant platform for evaluating long-term therapeutic efficacy in OC treatment.