International Journal of Nanomedicine (Dec 2023)
Combination of Chlorambucil and Mercaptopurine Show Effective Anti-Cancer Effects in Mice Model
Abstract
Weibing Xu,1 Yuxin Di,1 Shengjing Chu,1 Zixuan Wang,1 Haitao Long,1 Lumei Pu,1 Runtian Ma,1 Yanwei Wang2 1College of Science, Gansu Agricultural University, Lanzhou, 730000, People’s Republic of China; 2Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Astana, 010000, KazakhstanCorrespondence: Weibing Xu, College of Science, Gansu Agricultural University, No. 1 Yingmen Village, Anning District, Lanzhou, 730000, People’s Republic of China, Tel/Fax +86 931 7631212, Email [email protected]: Combination therapy employing multiple drugs has been shown to enhance the efficacy of cancer treatment. Chlorambucil (Chl) and 6-mercaptopurine (6MP) are the first-line medicines for chronic lymphocytic leukemia and ovarian cancer. However, both were limited by their short half-life of disintegration, unsatisfactory water solubility, and adverse reactions.Methods: In this work, the drug Chl and 6MP were introduced into the polymerized N-(2-hydroxypropyl) methacrylamide (polyHPMA) by pH and glutathione responsive linker to construct the polymer nanodrug delivery system for effective co-delivery.Results: The drug load capacities, release, morphology, and cytotoxicity of the pro-drug were systematic. The two drugs showed satisfactory synergism with a combination index of 0.81, and a better ability to induce apoptosis. In and ex vivo fluorescence imaging showed a rapid systemic distribution of the conjugate within mice, majorly metabolized by liver and kidneys and eliminated after 24 hr. No significant pathological damage was observed in the major organs. This polymeric prodrug system holds promise for improved therapeutic efficiency and reduced side effects through the synergistic delivery of various chemotherapeutics.Conclusion: The introduction of HPMA as a carrier not only enhanced the solubility and biocompatibilities of Chl and 6 MP but also improved their drug effect. This strategy might be a promising alternative for constructing multi-drug-release system. Keywords: polymer prodrug, co-delivery, chlorambucil, mercaptopurine, fluorescence images, cancer treatment
