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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 (&lt;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.

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