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.