Thermosensitive hydrogel used in dual drug delivery system with paclitaxel-loaded micelles for in situ treatment of lung cancer

Abstract

In this study, an in situ gel-based dual drug delivery system (PEG-PCL-PEG/DDP+MPEG-PCL/PTX, abbreviated as PDMP) was prepared through the combination of a cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG/DDP, PECE/DDP) and paclitaxel (PTX)-loaded polymeric micelles (average diameter of 20.1nm). PDMP is a free-flowing solution at room temperature and forms a stationary gel at body temperature, allowing it to serve as a drug depot for the in situ treatment of lung cancer. For in vivo experiments, the xenografted lung cancer model was used to evaluate the anti-tumor efficacy of the PDMP. The results suggested that PDMP is effective at inhibiting tumor growth and prolonging the survival time of tumor-bearing BALB/c nude mice. The survival time of the PDMP-treated group (53 days) is significantly higher than that of other groups (40 days from the free DDP+PTX group, 26 days from the blank PECE group, 25 days from the normal saline group, p<0.05). Immunohistochemical analysis revealed that tumors in the PDMP group had fewer microvessels and lower proliferation activity compared with those of the control group. Thus, PDMP may have great potential for in situ treatment of lung cancer by minimally invasive injection methods.

Keywords: Cisplatin; Lung cancer; Micelles; Paclitaxel; Thermosensitive hydrogel.