Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland.
Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Medyczna 9, 30-688 Kraków, Poland.
Molecules. 2024 Aug 12;29(16):3818. doi: 10.3390/molecules29163818.
Imatinib, a small molecule kinase inhibitor, is used as a cancer growth blocker. However, one of its most serious side effects is congestive cardiac failure. Reducing drug toxicity may be achieved through the use of drug delivery systems. Biocompatible metal-organic framework (MOF) materials, namely FeMIL-100 and FeMIL-101-NH, were employed as potential imatinib carriers. They efficiently delivered the drug as an anticancer agent while minimizing cardiotoxicity. Notably, the release of imatinib from FeMIL-100 was rapid in acidic conditions and slower in pH-neutral environments, allowing targeted delivery to cancer cells. The carrier's pH-dependent stability governed the drug release mechanism. Two release models-Korsmeyer-Peppas and Weibull-were fitted to the experimental data and discussed in terms of drug release from a rigid microporous matrix. Cytotoxicity tests were conducted on two cell lines: HL60 (a model cell line for acute myeloid leukemia) and H9c2 (a cell line for cardiomyocytes). Overall, the metal-organic framework (MOF) carriers mitigated imatinib's adverse effects without compromising its effectiveness.
伊马替尼是一种小分子激酶抑制剂，用作癌症生长抑制剂。然而，其最严重的副作用之一是充血性心力衰竭。通过使用药物传递系统可以降低药物毒性。生物相容性的金属有机骨架（MOF）材料，即 FeMIL-100 和 FeMIL-101-NH，被用作潜在的伊马替尼载体。它们有效地输送药物作为抗癌剂，同时最大限度地减少心脏毒性。值得注意的是，伊马替尼从 FeMIL-100 中的释放在酸性条件下很快，在 pH 中性环境中较慢，允许靶向递送到癌细胞。载体的 pH 依赖性稳定性控制药物释放机制。两种释放模型-柯斯迈尔-佩帕斯（Korsmeyer-Peppas）和 Weibull 被拟合到实验数据，并根据刚性微孔基质中药物的释放进行讨论。对两种细胞系进行了细胞毒性试验：HL60（急性髓细胞白血病的模型细胞系）和 H9c2（心肌细胞系）。总的来说，金属有机骨架（MOF）载体减轻了伊马替尼的不良反应，同时不影响其疗效。
