Studies have shown that treatment of pancreatic ductal adenocarcinoma (PDAC) with systemic administration of gemcitabine (GEM) is inhibited by excessive desmoplastic connective tissue surrounding the tumor. Ultrasound (US) insonification combined with drug-loaded poly lactic acid (PLA) microbubbles (MB) may circumvent this through targeted delivery to the tumor via increased permeability and lodging of GEM-loaded MB fragments in the tumor tissue. GEM-loaded MB were fabricated through a double emulsion process, and evaluated for efficacy as potential drug delivery agents. Acoustic and physical characterization suggest that GEM encapsulation does not significantly affect MB morphology or contrast activity (p > 0.23 compared with unmodified MB). Inertial cavitation upon exposure to US is not impacted by drug encapsulation, indicated by GEM-loaded MB exhibiting significant size reduction to fragments approximately 400 nm in diameter following insonation (p < 0.0001). In vitro cytotoxicity of these agents confirms GEM release from the MB in response to insonation. Free GEM resulted in a complete loss of PDAC cell viability at a concentration of 62.5nM, while concentrations of 500nM and above were needed for complete PDAC cell death from GEM-loaded MB. This result is encouraging, since PLA must hydrolyze to release the encapsulated GEM. Unmodified bubbles did initiate PDAC cell death. In vivo, administration of GEM-loaded MB is well tolerated. Xenograft MiaPaCa-2 PDAC tumors were grown in 60 athymic mice (12/group). Mice were then treated with one of five therapies and monitored for tumor growth. GEM-loaded MB provide substantial tumoral imaging enhancement before and after destructive pulses. However, no significant differences in tumor growth or mouse survival were observed among the treatment groups (p > 0.1). Encapsulation of GEM within the PLA shell of MB resulted in viable drug delivery agents for PDAC treatment. © 2017 IEEE.