Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with limited response to conventional chemotherapies such as paclitaxel (PTX) due to poor solubility, low bioavailability, and systemic toxicity. To address these limitations, this study explores mesenchymal stem cell (MSC)-derived exosomes as biocompatible, tumor-homing nanocarriers for PTX delivery. Exosomes were isolated from MSC-conditioned media using ultracentrifugation and tangential flow filtration (TFF), with TFF yielding 8 to 9-fold higher exosome recovery. Flow cytometry confirmed the presence of exosomal (CD63, CD81) and MSC (CD90) surface markers, while transmission electron microscopy and dynamic light scattering revealed spherical vesicles averaging ~160 nm in diameter with a zeta potential of approximately -28 mV. PTX was loaded into exosomes using ultrasonication, achieving an encapsulation efficiency of 31.3 ± 2.0%, and release studies showed an initial burst within 24 h followed by sustained release over 7 days. Blank exosomes exhibited no cytotoxicity toward PANC-1, BxPC-3, and HPNE cells, confirming their excellent biocompatibility. In contrast, PTX-loaded exosomes significantly enhanced cytotoxicity compared to free PTX, reducing IC(50) values from 12.48 nM to 7.55 nM in BxPC-3 cells and from 22.44 nM to 19.29 nM in PANC-1 cells and suppressed colony formation and spheroid growth more effectively. These findings demonstrate that MSC-derived exosomes can efficiently encapsulate and deliver PTX, enhancing its antitumor efficacy. This exosome-based platform offers a promising strategy to overcome pharmacological barriers and improve therapeutic outcomes in PDAC.