Abu Lila Amr Selim, Amran Mohammed, Tantawy Mohamed A, Moglad Ehssan H, Gad Shadeed, Alotaibi Hadil Faris, Obaidullah Ahmad J, Khafagy El-Sayed
Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Pharmaceutics. 2023 Jun 16;15(6):1755. doi: 10.3390/pharmaceutics15061755.
This study demonstrates high drug-loading of novel pyridine derivatives (S1-S4) in lipid- and polymer-based core-shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core-shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.
本研究表明，新型吡啶衍生物（S1 - S4）在基于脂质和聚合物的核壳纳米胶囊（LPNCs）中具有高载药量，可提高这些新型吡啶衍生物的抗癌效率并减轻其毒性。纳米胶囊采用纳米沉淀技术制备，并对其粒径、表面形态和包封率进行了表征。制备的纳米胶囊粒径范围为185.0 ± 17.4至223.0 ± 15.3 nm，药物包封率>90%。显微镜评估显示纳米胶囊呈球形，具有明显的核壳结构。体外释放研究表明，测试化合物从纳米胶囊中呈现双相和持续释放模式。此外，细胞毒性研究表明，与游离测试化合物相比，纳米胶囊对MCF - 7和A549癌细胞系均表现出优异的细胞毒性，表现为IC值显著降低。在艾氏腹水癌（EAC）实体瘤荷瘤小鼠模型中研究了优化的纳米胶囊制剂（载S4的LPNCs）的体内抗肿瘤功效。有趣的是，与游离S4或标准抗癌药物5 - 氟尿嘧啶相比，LPNCs中测试化合物（S4）的包封显著引发了更强的肿瘤生长抑制。这种增强的体内抗肿瘤活性伴随着动物寿命的显著延长。此外，载S4的LPNC制剂在治疗动物中耐受性良好，这通过没有任何急性毒性迹象或肝肾生化标志物变化得到证明。总体而言，我们的研究结果清楚地强调了载S4的LPNCs相对于游离S4在攻克EAC实体瘤方面的治疗潜力，可能是通过将足够浓度的包封药物有效递送至靶位点实现的。
