Combination of Chlorambucil and Mercaptopurine Show Effective Anti-Cancer Effects in Mice Model

Xu W. Di Y. Chu S. Wang Z. Long H. Pu L. Ma R. Wang Y.
2023 Dove Medical Press Ltd

International Journal of Nanomedicine
2023 #18 8131 - 8141 pp.

Background: 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.

cancer treatment , chlorambucil , co-delivery , fluorescence images , mercaptopurine , polymer prodrug

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College of Science, Gansu Agricultural University, Lanzhou, 730000, China
Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Astana, 010000, Kazakhstan

College of Science
Department of Chemical and Materials Engineering

10 лет помогаем публиковать статьи Международный издатель

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