Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Tiejun Zhao,¹ Hezhong Chen,¹ Yuchao Dong,² Jiajun Zhang,¹ Haidong Huang,² Ji Zhu,¹ Wei Zhang<sup>2

1</sup>Institute of Cardiothoracic Surgery, ²Respiratory Department, Changhai Hospital, Shanghai, People's Republic of China


Abstract: In order to improve the therapeutic efficacy and minimize the side effects of lung cancer chemotherapy, the formulation of paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles (PTX-loaded [PGA-co-PCL]-b-TPGS_2k NPs) was prepared. The novel amphiphilic copolymer (PGA-co-PCL)-b-TPGS_2k was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded (PGA-co-PCL)-b -TPGS_2k NPs were characterized in terms of size, size distribution, zeta potential, drug encapsulation, surface morphology, and drug release. In vitro cellular uptakes of NPs were investigated with confocal laser scanning microscopy, indicating the coumarin 6-loaded (PGA-co-PCL)-b -TPGS_2k NPs could be internalized by human lung cancer A-549 cells. The antitumor effect of PTX-loaded NPs was evaluated, both in vitro and in vivo, on an A-549 cell tumor-bearing mouse model via intratumoral injection. The commercial PTX formulation Taxol was chosen as the reference. Experimental results showed that the PTX-loaded NPs possessed higher cytotoxicity and could effectively inhibit the growth of tumor. All the results suggested that amphiphilic copolymer (PGA-co-PCL)-b -TPGS_2k could act as a potential biological material for nanoformulation in the treatment of lung cancer.

Keywords: (PGA-co-PCL)-b TPGS_2k, paclitaxel, nanoparticles, drug delivery, lung cancer