Alghazwani Yahia, Venkatesan Krishnaraju, Prabahar Kousalya, El-Sherbiny Mohamed, Elsherbiny Nehal, Qushawy Mona
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
Pharmaceutics. 2023 Jan 16;15(1):302. doi: 10.3390/pharmaceutics15010302.
In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca ions causes cells to undergo apoptosis. Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half.
在当前研究中,评估了负载六甲蜜胺(ALT)的生物活性羟基磷灰石纳米颗粒(HA-NPs)的联合抗肿瘤疗效。溶血实验结果以及MTT测试中观察到的最大IC值证实了HA具有良好生物相容性这一众所周知的事实。HA-NPs采用化学沉淀法制备。进行了体外释放研究,结果表明负载六甲蜜胺的羟基磷灰石纳米颗粒(ALT-HA-NPs)具有药物缓释特性。使用JURKAT E6.1细胞系的MTT测定、细胞摄取研究以及使用Wistar大鼠进行的体内药代动力学测试表明,ALT-HA-NPs易于被细胞吸收。ALT-HA-NPs在ALT浓度为十分之一时表现出与游离ALT相当的细胞毒性,这表明Ca离子的作用与从载体获得的抗癌药物之间存在假定的协同作用。有人提出细胞内Ca离子的增加会导致细胞凋亡。在Balb/c小鼠的艾氏腹水模型中,在肿瘤消退试验中显示出相当的协同疗效。虽然ALT-HA-NPs能够使肿瘤大小缩小六倍,但游离ALT仅能使肿瘤体积减少一半。