Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2023 May 8;28(9):3974. doi: 10.3390/molecules28093974.
Lung cancer is the main cause of cancer-related mortality globally. Erlotinib is a tyrosine kinase inhibitor, affecting both cancerous cell proliferation and survival. The emergence of oncological nanotechnology has provided a novel drug delivery system for erlotinib. The aims of this current investigation were to formulate two different polyamidoamine (PAMAM) dendrimer generations-generation 4 (G4) and generation 5 (G5) PAMAM dendrimer-to study the impact of two different PAMAM dendrimer formulations on entrapment by drug loading and encapsulation efficiency tests; to assess various characterizations, including particle size distribution, polydispersity index, and zeta potential; and to evaluate in vitro drug release along with assessing in situ human lung adenocarcinoma cell culture. The results showed that the average particle size of G4 and G5 nanocomposites were 200 nm and 224.8 nm, with polydispersity index values of 0.05 and 0.300, zeta potential values of 11.54 and 4.26 mV of G4 and G5 PAMAM dendrimer, respectively. Comparative in situ study showed that cationic G4 erlotinib-loaded dendrimer was more selective and had higher antiproliferation activity against A549 lung cells compared to neutral G5 erlotinib-loaded dendrimers and erlotinib alone. These conclusions highlight the potential effect of cationic G4 dendrimer as a targeting-sustained-release carrier for erlotinib.
肺癌是全球癌症相关死亡的主要原因。厄洛替尼是一种酪氨酸激酶抑制剂，影响癌细胞的增殖和存活。肿瘤纳米技术的出现为厄洛替尼提供了一种新的药物传递系统。本研究的目的是制备两种不同的聚酰胺-胺（PAMAM）树枝状大分子——第四代（G4）和第五代（G5）PAMAM 树枝状大分子——研究两种不同 PAMAM 树枝状大分子配方对包封的影响，通过药物载药量和包封效率测试进行评价；评估各种特性，包括粒径分布、多分散指数和zeta 电位；并评估体外药物释放以及原位人肺腺癌细胞培养。结果表明，G4 和 G5 纳米复合物的平均粒径分别为 200nm 和 224.8nm，多分散指数值分别为 0.05 和 0.300，zeta 电位值分别为 11.54mV 和 4.26mV。比较原位研究表明，与中性 G5 载有厄洛替尼的树枝状大分子和单独的厄洛替尼相比，阳离子 G4 载有厄洛替尼的树枝状大分子对 A549 肺细胞具有更高的选择性和增殖抑制活性。这些结论突出了阳离子 G4 树枝状大分子作为厄洛替尼靶向缓释载体的潜在作用。
