Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer

TANG Lan1 ZHU Zhuan-feng1 CAO Li-peng1 SHEN Miao1 GAO Yan1 TU Chao-jie1 ZHANG Zhen-hai2 SHAN Wei-guang1

(1.College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang Province, China 310014)
(2.Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China 210028)

【Abstract】Polysaccharide from Ganoderma applanatum (PGA) has the activities of resisting tumor and enhancing immune function. The anti-tumor effect of its intratumoral injection has not been reported. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after protein removal by Sevage method. The total PGA was about 63%. The combination of PGA and paclitaxel (PTX) showed a synergistic effect on cytotoxicity of 4T1 cells at a low concentration in vitro. In addition, the growth curve of 4T1 cells showed that PGA could retard the growth of 4T1 cells gradually. The PGA thermosensitive gel (PGA-TG) was prepared by using poloxamer 188 and 407. The gel temperature was 36 °C, and the PGA-TG could effectively slow down the release rate of PGA in vitro. With 4T1 breast cancer-bearing mice as a model, this study evaluated the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound PTX (nab-PTX). In high- and low-dose PGA-TG groups, each mouse was given with 2.25 and 1.125 mg of PGA respectively, twice in total, and the dose of PTX was 15 mg·kg−1, once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high-dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in the low-dose PGA-TG combined with nab-PTX group, and 68.10% in the high-dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in the high-dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in the nab-PTX group (P < 0.05). The results showed that PTX therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4T1 mice and reduce the side effects of chemotherapy.

【Keywords】 polysaccharide from Ganoderma applanatum; thermosensitive gel; paclitaxel; breast cancer; combination therapy;

【DOI】

【Funds】 National Natural Science Foundation of China (81403117)

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This Article

ISSN:1001-5302

CN:11-2272/R

Vol 45, No. 11, Pages 2533-2539

June 2020

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Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References