Eudragit S100 prepared pH-responsive liposomes-loaded betulinic acid against colorectal cancer in vitro and in vivo

Abstract

This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3⁺ cells in tumor tissues, and the proportion of CD8⁺ cells in CD3⁺ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.

Keywords:

• Betulinic acid
• liposomes
• Eudragit S100
• pH targeting
• immunity
• colorectal cancer

Acknowledgements

This article is distributed under the terms of noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.

Author contributions

Gang Wang designed the experiments; Yang Yu performed the experiments; Yang Yu prepared Figures 1–3. Yang Yu analyzed the experimental results and prepared Figures 4–8. Ke Xu analyzed the sequencing data and developed the analysis tools. Gang Wang wrote the manuscript while Pei-Hao Yin revised it.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the National Natural Science Foundation of China [No. 81673827] and Shanghai National Chinese Medicine Innovation Key Talent Training Project.