School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; Translational Research Center in Oncohaematology, Geneva, Switzerland.
Rue Michel-Servet 1, CMU, 1211 Geneva 4, Switzerland.
J Control Release. 2023 Jun;358:59-77. doi: 10.1016/j.jconrel.2023.04.006. Epub 2023 Apr 28.
Fixed-drug combinations have been used for the treatment of cancer. Current anticancer therapies, however, tend to induce resistance and provoke important toxicity. Therefore, there is still a need for further optimized treatments that would also take into account drug-drug interactions. Tyrosine kinase inhibitors (TKIs) and Histone deacetylase inhibitors (HDACIs) are two anticancer drug classes currently used separately in clinical practice. Those drug classes are currently being investigated in clinical trials. Several findings confirm the safety and tolerability of these treatments accompanied by clinical improvement. The activity and specificity of drug combinations can be further improved by employing appropriate drug delivery systems, such as nanocarrier systems. The different pharmacokinetic profiles of each drug may lead to a loss in synergistic effects, affecting treatment efficiency. Several combinations of either TKI or HDACI with an anticancer drug of another class co-loaded inside liposomal carriers are being investigated in vivo and show promising results in terms of efficacy and safety. In this review we discuss strategies for the delivery of synergistic drug combinations for cancer treatment.
固定药物组合已被用于癌症治疗。然而，目前的癌症治疗方法往往会诱导耐药性并引发严重的毒性。因此，仍然需要进一步优化治疗方法，同时考虑药物相互作用。酪氨酸激酶抑制剂（TKIs）和组蛋白去乙酰化酶抑制剂（HDACIs）是目前在临床实践中分别使用的两种抗癌药物类别。这些药物类别目前正在临床试验中进行研究。多项研究结果证实了这些治疗方法的安全性和耐受性，同时伴有临床改善。通过使用适当的药物递送系统，如纳米载体系统，可以进一步提高药物组合的活性和特异性。由于每种药物的药代动力学特征不同，可能会导致协同作用丧失，从而影响治疗效果。目前正在体内研究将 TKI 或 HDACI 与另一种抗癌药物联合装入脂质体载体的组合，在疗效和安全性方面显示出有希望的结果。在这篇综述中，我们讨论了用于癌症治疗的协同药物组合的递药策略。
