Evaluation of the therapeutic effect of melittin peptide on the ulcerative colitis mouse model.

BACKGROUND: Ulcerative colitis (UC) is considered one of the most prevalent inflammatory bowel diseases (IBDs). However, due to the lack of satisfying efficacy of conventional therapies and their side effects, there is still a need for more efficient therapeutic agents. Melittin is a small peptide derived from bee venom, which shows potent anti-inflammatory activity. The present investigation aimed to assess the anti-inflammatory effect of melittin peptide alone and in co-therapy with sulfasalazine as a standard therapy on dextran sulfate sodium (DSS)-induced colitis models. MATERIAL AND METHODS: We used DSS to induce UC in C57BL/6 male mice. We investigated the effect of melittin peptide alone and in combination with sulfasalazine on improving the clinical symptoms among DSS-induced colitis models. Finally, we employed histological investigation to show the therapeutic effect of melittin on attenuating the pathological damage of colon tissue caused due to DSS-induced inflammation in colitis models. RESULTS: Our findings demonstrated that melittin peptide alone and in combination with sulfasalazine dramatically cured the clinical UC. Moreover, we observed that this peptide almost eliminated the histological damage of colon tissue in colitis, while significantly reducing the inflammation in colon tissue. Meanwhile, our results demonstrated that this peptide had an antioxidant effect through the disruption of the oxidant/antioxidant balance. CONCLUSION: All these findings suggest that melittin peptide has an anti-inflammatory effect and can probably be considered a novel therapeutic agent for UC. Furthermore, our results demonstrated that this peptide can enhance the therapeutic effects of conventional therapy while attenuating the adverse effects of conventional agents.

Optimization of post-insertion method to conjugate Doxil with anti-CD133 monoclonal antibodies: Investigating the specific binding and cytotoxicity to colorectal cancer cells in vitro.

In this paper, Doxil coupled with anti-CD133 monoclonal antibodies made by either routine or optimized post-insertion technique, were compared with respect to their size, drug leakage, release pattern and the number of antibodies conjugated per single liposome. The results demonstrated that the number of antibodies conjugated per liposome in the optimized post-insertion technique was almost two times more than those in the routine post-insertion method. However, the drug release and leakage pattern was almost similar between the two methods. Furthermore, anti-tumor activity and therapeutic efficacy of the preferred CD133-targeted Doxil with Doxil was compared in terms of their in vitro binding, uptake, internalization and cytotoxicity against HT-29 (CD133+) and CHO (CD133-) cells. Flow cytometry analyses and confocal laser scanning microscopy results exhibited a significantly higher cellular uptake, binding and internalization of CD133-targeted Doxil in CD+133 cells relative to Doxil. Cytotoxicity results revealed a lower in vitro inhibitory concentration for CD133-targeted Doxil compared to Doxil. However, CHO (CD133-) cells displayed a similar uptake and in vitro cytotoxicity for both CD133-Doxil and non-targeted Doxil. Therefore, the results of this study can exhibit that specific recognition and binding of antibodies with CD133 receptors on HT-29 cells can result in enhanced cellular uptake, internalization and cytotoxicity. The research suggests further investigation for in vivo studies and may offer proof-of-principle for an active targeting concept.