As is well-known, due to the complex pathogenesis of pancreatic cancer, monotherapy alone is no longer sufficient to meet current treatment goals. Combination drug therapy shows greater potential compared to monotherapy. Paclitaxel (PTX) and gemcitabine (GEM) are frequently used together to treat various types of cancers. However, the two drugs differ significantly in their physical and chemical properties, and simple coadministration can lead to severe toxic side effects. In this study, liposome technology was employed to coencapsulate paclitaxel palmitate (PTX-PA) and gemcitabine hydrochloride (GEM) to create paclitaxel palmitate and gemcitabine hydrochloride coloaded liposomes (PTX-PA/ GEM-L), which were subsequently characterized. A series of in vivo and in vitro experiments were conducted to evaluate their stability, safety, and antipancreatic cancer activity. The particle size of PTX-PA/GEM-L was 99 ± 1 nm (x ̅ ± s, n = 3), with a PDI of 0.17 ± 0.01 (x ̅ ± s, n = 3) and a zeta potential of −33.37 ± 0.15 mV. Notably, PTX-PA/GEM-L exhibited a sustained release profile in PBS, largely unaffected by pH changes. The cumulative release rate of GEM from PTX-PA/GEM-L after 48 h was between 57% and 60%. The formulation demonstrated good stability when stored in the dark at low temperatures. Additionally, it was found to be nonhemolytic and nonirritant to blood vessels, making it suitable for intravenous injection. Compared to the free GEM group, free PTX-PA group, and the physical mixture of GEM and PTX-PA, PTX-PA/GEM-L demonstrated an extended drug half-life, longer in vivo circulation time, better targeted accumulation at tumor sites, lower toxicity, and a more potent antitumor effect. This study demonstrates that the PTX-PA and GEM coloaded liposomal drug delivery system has superior in vivo antitumor efficacy compared to the simple combination of the two drugs, providing an effective combined treatment strategy for the clinical management of pancreatic cancer.
